Estrogen deficiency and progressive hearing loss (HL) are significant concerns in individuals with Turner syndrome (TS). However, whether childhood estrogen deficiency increases HL risk and whether estrogen replacement therapy (ERT) prevents hearing deterioration are still unclear. This prospective cohort study recruited children with TS from a tertiary referral center between 2016 and 2024. All participants received standardized recombinant human growth hormone therapy. Longitudinal monitoring data of hormone levels, metabolic parameters, and annual audiological examinations were recorded. The primary analysis used a multivariate Cox model to estimate the adjusted hazard ratio of hearing loss between estrogen-deficient and estrogen-normal TS patients without prior exogenous estrogen exposure. The secondary analysis compared annual pure tone average (PTA) and its changes between the ERT and non-ERT groups in a substudy. Among 87 prepubertal pediatric TS patients, 48 (55.2%) were estrogen-deficient, 38 HL events occurred over 35-month median follow-up. The estrogen-deficient group had higher HL incidence (27 cases, 56.3%; 20.6/100 person-years [PY]) versus estrogen-normal (11 cases, 28.2%; 8.6/100 PY), with estrogen deficiency independently increasing HL risk (HR = 2.93; 95%CI:1.21-7.12). Notably, estrogen deficiency also independently predicted abnormal DPOAE with an even higher effect size (HR = 3.98, 95% CI: 1.35-11.76). The substudy found that initiating ERT at age of 12 significantly preserve auditory function, with the ERT group showing markedly lower PTA and slower hearing deterioration (-1.24 dB/y vs. 1.13 dB/y right ear; -1.85 dB/y vs. 1.04 dB/y left ear, P = 0.001). Childhood estrogen deficiency is a modifiable risk factor. Initiating ERT around early adolescence may help hearing preservation. ChiCTR2300068063. National Natural Science Foundation of China (82173154 and 82471155), Fundamental Research Funds for the Central Universities, Clinical Research 5010 Program, Sun Yat-sen University: 2024004.

Cochlear implant (CI) insertion trauma, as evidenced by fracture of the osseous spiral lamina (OSL), is associated with localized "dead zones" and focal spiral ganglion neuron (SGN) loss. Hearing and structure preservation approaches to CI insertion aim to minimize trauma and preserve residual SGNs. In cases of significant insertion trauma, peripheral axons running through the bony OSL inherently become damaged if the OSL is fractured. The current investigation sought to determine if the relative location of OSL fracture was associated with focal areas of SGN loss. Five adult ears from the Mass Eye and Ear Otopathology Laboratory were identified with OSL fractures. When available, contralateral ears were also analyzed for comparison. Digitized e-Slides were used to create 3D cochlear reconstructions, and a coordinate system relative to the round window allowed for % distance along Rosenthal canal (RC) assignment of SGNs and OSL fracture locations. Abrupt changes in SGN density, defined as a drop >50% within a 5% segment along RC were used as criteria for a significant and focal SGN loss. Insertion trauma in the form of electrode translocation and spiral ligament (SL) perforation was also characterized. OSL fracture lengths ranged from approximately 72 to 109 degrees about the modiolus, with a median fracture length of 75 degrees. Total SGN counts ranged from 16,810 to 22,260. Abrupt and focal drops of >50% in SGN density occurred in all 5 temporal bones with OSL fracture. In 3 of the cases, there were areas of localized "dead zones" at or immediately adjacent to the OSL fracture site, whereas in the remaining 2 cases, drops were seen in various areas across the cochlea. The case with the longest fracture demonstrated nearly a complete loss of neurons apical to the deepest fracture location. Ears with OSL fractures demonstrate a higher number of "dead zones" than the contralateral ears used for comparison, with median values of 3 and 2, respectively. Cases with an OSL fracture, electrode translocation, and SL perforation demonstrated a notably higher number of "dead zones" (median = 3) as compared with ears with only 1 or 2 CI insertional trauma injuries (median = 2). In temporal bones from CI patients, OSL fractures explain some-but not all-of the abrupt SGN loss observed following traumatic CI insertions. Distinct regions of SGN density observed across the length of these cochlea indicate multifactorial processes likely contribute to relative SGN "dead zones."

Combined Transpetrosal Meningioma Resection with Sacrifice of the Superior Semicircular Canal with Hearing Preservation and Reconstruction of the Labyrinth

Abstract Researchers have attempted to predict hearing preservation for vestibular schwannoma (VS) patients, with preoperative hearing scores and tumor size identified as useful predictors for hearing preservation. However, prior studies have not directly included magnetic resonance (MR) images in their predictive models, instead using secondary imaging measurements and other clinical features. Here, we created a deep learning model that directly incorporates preoperative images to predict VS patients' hearing preservation. Using 97 patients who underwent VS hearing preservation surgery at our institution, we modeled hearing preservation with clinical and image feature-based logistic regression (LR) and an image-based convolutional neural network (CNN) model, with or without clinical features added. LR models that included tumor size and preoperative hearing provided good hearing preservation discrimination (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] AUC = 0.79; Word Recognition Score [WRS] Area under curve (AUC) = 0.77). Two-channel MRI inputs were used for a 3D CNN, ResNet50, and a hybrid ResNet50 including tumor size and preoperative hearing. The hybrid model was our most accurate and was comparable with existing models (four-fold mean receiver operating characteristic [ROC] = 0.71; best ROC = 0.85). Previously described MRI features were not significantly correlated with hearing outcomes. We confirm that the first deep learning model to directly incorporate preoperative images and clinical features for VS patients can help predict hearing preservation. This type of model may help risk-stratify VS patients during surgical planning, with the goal of ultimately improving surgical outcomes for patients.

ImportanceOpening the cochlear‒carotid recesses through the endoscope-assisted modified translabyrinthine approach to treat lesions in the petrous apex has been demonstrated to preserve the cochlea and hearing. The objective parameters of recesses and their relationships with vital structures were fundamental to the effective application of this technique.ObjectiveHerein, we present a quantitative analysis of cochlear‒carotid recesses on high-resolution computed tomography (HRCT) images and discuss their implications for hearing preservation in the surgical management of massive petrous bone cholesteatomas (PBCs).DesignObservational study.ParticipantsTwenty samples (40 sides) obtained between April and June 2021 radiographically via HRCT.MethodsHRCT images of 40 ears were acquired at 0.60 mm thickness and processed via Mimics. The intrinsic structures of the temporal bone were reconstructed in a 3D view. The morphological data were precisely measured on multiplanar reconstructed images. In addition, clinical implications were demonstrated in one patient with massive temporal bone cholesteatoma.ResultsA 3D model of the cochlear‒carotid recesses was reconstructed. The recesses were essentially divided into 2 parts, namely, the triangle anterior and superior to the cochlea (TASC) and the triangle anterior and inferior to the cochlea (TAIC). The size of the cochlear‒carotid recesses varied widely among the samples. The TASC was accessible in 80% of the samples via a conventional ear endoscope with a diameter of 3 mm, while the applicability of the TAIC was 62.5%. We further discovered that the low position of the trigeminal nerve impression and the small distance between the cochlea and the jugular bulb suggested narrow recesses. The thickness of the compact bone shell of the cochlear lumen acted as a safe drilling divider.ConclusionsHRCT and 3D reconstruction clearly displayed cochlear‒carotid recesses. For patients with massive PBC, the use of an endoscope to open recesses is feasible in the majority of cases and increases the possibility of preserving the structure and function of the cochlea. Individualized preoperative measurements of cochlear‒carotid recesses via HRCT could help surgeons perform safe and accurate dissection.

Intracochlear electrocochleography (ECochG) in cochlear implant (CI) recipients is a potential tool for monitoring cochlear function during and after electrode array (EA) insertion. However, mechanisms underlying ECochG amplitude variations along the cochlear duct, and their significance for hearing preservation (HP), remain unclear. Therefore, a longitudinal study was conducted to monitor maximum ECochG amplitude and its tonotopic location from EA insertion to 1 yr postimplantation. It was hypothesized that changes in maximum amplitude (>30%) and/or shifts in its location (>1 octave) across timepoints reflect intracochlear alterations associated with residual hearing changes. ECochG recordings were obtained in 80 adult CI recipients with measurable residual hearing. For Contour Advance (CI612) and Slim Straight (CI622) arrays (Cochlear Ltd.), recordings were taken from every second intracochlear electrode. For HiFocus SlimJ and MidScala arrays (Advanced Bionics LLC), recordings were obtained from all electrodes. Measurements were conducted at four timepoints: (1) intraoperatively, during EA insertion (Intraop1), (2) intraoperatively, immediately after full insertion (Intraop2), (3) approximately 7 wk after surgery (Postop1), and (4) approximately 1 yr after surgery (Postop2). 500 Hz tone bursts were used for acoustic stimulation and the magnitude of the difference between responses to alternating-polarity stimuli was analyzed. Tonotopic electrode locations were determined from postoperative cone beam computed tomography scans. Pure-tone audiograms were obtained preoperatively and at approximately 7 wk and 1 yr postoperatively. HP was determined using the HEARRING group formula. Maximum ECochG amplitudes remained largely stable intraoperatively, with no significant difference between Intraop1 and Intraop2 in complete-case analysis (n = 44). In contrast, a significant decrease in maximum amplitude was observed between Intraop2 and Postop1 (p < 0.001). Participants with >30% amplitude reduction between the 2 intraoperative recordings (Intraop1 versus Intraop2) did not differ significantly in HP from those with stable amplitudes. However, those showing a >30% reduction in the early postoperative period (Intraop2 versus Postop1) showed significantly lower HP (p = 0.028). Nonapical peak location during Intraop1 occurred in 41% of the cases, although tonotopic location of the maximum peak during insertion monitoring (Intraop1) did not show a relationship with HP. Tonotopic location shifts of the maximum amplitude (>1 octave) were observed in a small subset of cases between consecutive recordings up to Postop2. However, peak location changes (apical, basal, stable) were not associated with significant differences in HP. Our results suggest that nonapical peak patterns are not necessarily markers of insertion trauma and may instead reflect variability in cochlear integrity (e.g., dead regions). Peak location during insertion monitoring was not associated with postoperative HP, and both maximum amplitude and tonotopic peak location remained stable intraoperatively. In contrast, early postoperative reductions in ECochG amplitude were common and associated with HP, highlighting the need to investigate strategies to minimize early intracochlear reactions. Overall, the study demonstrates the value of ECochG for monitoring intracochlear processes over time.

Introduction Electrocochleography (ECochG) has emerged as a valuable intra-operative monitoring tool in cochlear implantation, particularly for preserving residual hearing. This study evaluates the correlation between intra-operative ECochG responses and post-operative hearing outcomes in cochlear implant recipients. Materials and methods A cohort of 23 adult subjects with residual acoustic hearing in the low frequencies undergoing cochlear implantation were included. All subjects received Advanced Bionics' HiRes Ultra 3D implants and HiFocus SlimJ electrode arrays, with ECochG monitored during surgery via the AIM system. Intra-operative ECochG responses were categorized into positive, negative, and flat track patterns. Post-operative hearing outcomes were assessed at 1, 3, 6, and 12 months, focusing on hearing preservation. Results In 70% of participants, recordable ECochG responses were obtained, with positive track patterns correlating with significantly lower mean hearing loss (17.1 dB) compared to negative (27.5 dB) and flat patterns (30.7 dB). At the 12-month post-operative mark, 83% of all participants retained complete or partial hearing preservation, with 100% complete or partial preservation in subjects exhibiting positive track patterns. Discussion This study highlights the association between intra-operative ECochG responses and post-operative acoustic hearing outcomes, indicating its potential as a monitoring tool during cochlear implantation. While ECochG provides real-time insights into cochlear function, this observational study did not evaluate whether acting on ECochG feedback improves outcomes. Therefore, these findings should be interpreted as correlational rather than interventional. Future research should include larger cohorts and investigate whether integrating ECochG-guided strategies into surgical protocols can enhance hearing preservation and long-term outcomes.

Menière's disease is achronic inner ear disorder characterized by recurrent vertigo attacks, tinnitus, and fluctuating hearing loss, which may progress to severe sensorineural hearing impairment in asubset of patients. Since 2015, international consensus criteria distinguish between definite and probable disease. Current therapeutic strategies follow astepwise approach, ranging from non-ablative to ablative interventions. Cochlear implantation (CI) has emerged as an effective option for auditory rehabilitation and has also shown beneficial effects on vertigo and tinnitus. Combined strategies with endolymphatic sac surgery are discussed, while labyrinthectomy with simultaneous CI represents ahighly effective yet irreversible intervention. Particular challenges arise in bilateral cases, where radiological endotyping (e.g., hypoplastic vestibular aqueduct type) may improve future treatment planning. Evidence demonstrates that CI is feasible after ablative procedures as well as in unilateral Menière's disease with hearing preservation, resulting in significant improvements in quality of life. Systematic reviews confirm the safety and efficacy of CI, establishing its central role in the management of advanced disease stages. Early developments of vestibulocochlear implants (VCI) additionally open perspectives for combined auditory and vestibular rehabilitation, although clinical application remains experimental.

Background Patients with smaller vestibular schwannoma (VS) with preserved hearing can be subjected to hearing preservation surgery using the Middle Cranial Fossa (MCF) approach. Aims/Objectives We aimed to evaluate hearing outcome postoperatively and more than 10 years after MCF surgery. Materials and methods Eighty-four patients with sporadic unilateral VS treated with MCF surgery between 1998 and 2020 at a single tertiary centre, were retrospectively studied. Pure tone audiometry and word recognition scores (WRS) preoperatively, postoperatively, and after > 10 years of follow-up, were analysed. Results Sixty (71%) patients had preserved hearing function after MCF surgery. Twenty-three of the 60 patients were followed up for >10 years after surgery. Hearing outcomes of the tumour ear after >10 years of follow up were as follows: median pure tone average (PTA): 61 decibel hearing level (dB HL) (range 6–94 dB HL), and median WRS 71% (range: 0–98%). The age-related decline in pure tone audiometry thresholds was not significantly different between the tumour and contralateral ears Conclusions and significance MCF surgery offers the possibility of retaining hearing function even after >10 years of surgery in patients with preserved hearing. Additional hearing loss at the long-term follow-up was bilateral and symmetrical.

A fast-slow liposome based "orthodox-unexpected interplay" strategy for bacterial otitis media and associated hearing loss.

Rogers syndrome (thiamine-responsive megaloblastic anemia, TRMA) is a rare autosomal recessive disorder caused by mutations in SLC19A2 and is characterized by megaloblastic anemia, diabetes and sensorineural deafness. Therefore, it is of interest to review the effect of early thiamine therapy on recovery of hematologic function, preservation of hearing and glycemic control. Available data shows that anemia reversed consistently with early thiamine, glycemic control improved when treatment was initiated before β-cell exhaustion and hearing loss almost never improved once it had occurred. Thus, early administration of thiamine is critical to hematologic recovery and to partial metabolic benefit, but is not uniformly preventive of deafness.

Hearing preservation and restoration surgery in NF2-related schwannomatosis.

Background Ferritin, a key iron-storage and antioxidant protein, is integral to iron metabolism. Its association with hearing loss remains unclear. Objectives This study aimed to investigate the association between serum ferritin levels and hearing loss in U.S. adults and explore potential causal relationships using Mendelian Randomization (MR). Methods We analyzed 2,971 participants from NHANES 1999–2002 using weighted multivariable logistic regression to assess associations between serum ferritin levels (high, normal, and low) and different frequencies of hearing loss. Stratified analyses were conducted. Bidirectional MR was performed using GWAS summary statistics to infer causal associations for sensorineural/conductive hearing loss. Results After full adjustment, high serum ferritin was associated with a significantly lower risk of high-frequency hearing loss (HFHL) (OR = 0.600 [0.390, 0.922]), especially in younger participants (20–44 years) and males. MR analysis supported a causal protective role of ferritin against sensorineural hearing loss (OR = 0.860 [0.765, 0.968]). Conclusions Higher serum ferritin levels are observationally associated with a reduced risk of HFHL. Genetic analyses further suggest a protective causal relationship between ferritin and sensorineural hearing loss. Significance These findings suggest ferritin may be a biomarker or potential intervention target for hearing preservation. Further prospective and experimental validation of these associations is warranted.

To evaluate hearing outcomes after treatment with stereotactic radiosurgery (SRS) for sporadic vestibular schwannoma (VS) among patients with baseline 100% word recognition scores (WRS). Historical cohort. Tertiary academic medical center. Patients with 100% WRS on audiometric testing at initial treatment with SRS. Gamma Knife SRS. Rate of maintaining serviceable hearing (SH), defined as American Academy of Otolaryngology-Head and Neck Surgery hearing class A or B. In total, 125 patients had 100% WRS at SRS for sporadic VS. Median age at SRS was 56 years (IQR: 51 to 62) and median pure tone average (PTA) at SRS was 20 dB HL (IQR: 13 to 31). Sixty-eight patients progressed to non-SH at a median of 3.4 years after SRS (IQR: 1.0 to 8.6); the median duration of follow-up for the 57 patients who maintained SH was 5.1 years (IQR: 2.8 to 9.6). Rates of maintaining SH (95% CI, number still at risk) at 1, 3, 5, 7, and 10 years after SRS were 88% (82 to 94, 101), 75% (68 to 84, 81), 61% (53 to 71, 55), 58% (49 to 68, 43), and 44% (35 to 56, 26), respectively. Each 10-dB HL increase in PTA at SRS was associated with a 52% increased risk of progression to non-SH (hazard ratio: 1.52, 95% CI: 1.24-1.87, P<0.001). Despite having 100% pretreatment WRS, most patients with sporadic VS treated with SRS experienced clinically significant hearing decline over time. Even among this cohort of patients with excellent baseline hearing, at 10 years after treatment, only 44% of patients maintained SH.

Robotic-assisted electrode array (EA) insertion is a promising technique that may enhance preservation of residual acoustic hearing after cochlear implant (CI) surgery. The purpose of this study is to evaluate the impact of robotic-assisted EA insertion on rates of delayed-onset hearing loss (DOHL). Sixty (Advanced Bionics [AB]: 30, MED-EL: 30) adult patients underwent CI surgery with manual EA insertion and 29 (AB: 13, MED-EL: 16) with robotic-assisted insertion using the iotaSOFT system. The primary outcome variable was longitudinal change in low frequency pure-tone average (LFPTA). DOHL was defined as a decrease in LFPTA of > 10 dB compared to previous best postoperative LFPTA. Twenty-two (37%) out of the 60 subjects in the manual cohort and two (7%) out of the 29 subjects in the robotic-assisted cohort had DOHL over the entire length of available follow-up (p = 0.002, Fisher's exact test, two-tailed). When evaluating DOHL results for subjects who had LFPTA data at 12 months (±4 weeks) post initial activation, 11 (29%) out of the 38 (AB: 15, MED-EL: 23) subjects in the manual cohort and zero (0%) out of the 18 (AB: 8, MED-EL: 10) subjects in the robotic-assisted cohort had DOHL (p = 0.011, Fisher's exact test, two-tailed). The number needed to treat was 4. Robotic-assisted EA insertion is associated with a clinically meaningful reduction in rates of DOHL. Preservation of residual acoustic hearing is a critical goal in CI surgery, and robotic-assisted EA insertion contributes towards achieving this goal.

Hearing loss representsa major global health challenge.Particularly,ototoxicity induced by cisplatin and aminoglycosides remains a significantclinical problem. In this study, we synthesized and characterizedmagnetite nanoparticles (Fe3O4) functionalizedwith protocatechuic acid (Fe3O4@3,4-DHAB) andwith protocatechuic acid plus sodium citrate (Fe3O4@3,4-DHAB@NaCitrate) and evaluated their effects on auditoryHouse Ear Institute-Organ of Corti 1­(HEI-OC1) cells exposed to cisplatinand gentamicin. The nanoparticles exhibited good biocompatibility,maintaining a cell viability above 85% even at high concentrations.Functionalized formulations, particularly Fe3O4@3,4-DHAB, mitigated drug-induced loss of viability, preserved mitochondrialmembrane potential, and reduced senescence-associated activity. Theseprotective effects are consistent with the intrinsic antioxidant andanti-inflammatory properties of protocatechuic acid. Although limitedto an in vitro model, our findings provide preliminary evidence thatrational surface engineering of magnetic nanoparticles representsa viable strategy for mitigating ototoxic stress. This study buildsupon our previous work demonstrating the role of PCA-functionalizedFe3O4 nanoparticles in modulating immune responsesand promoting interactions with adipose-derived stem cell phenotypes.Together, these results underscore the potential of multifunctionalnanomaterials to contribute to the development of novel approachesfor hearing preservation.

Labyrinthine fistula is a complication of ear cholesteatoma that increase the risk of sensorineural hearing loss. The management of the fistula must be done contextually with mastoidectomy by: leaving cholesteatoma matrix over the fistula, or remove the matrix reconstructing the defect. Objective: analysis of the two techniques to treat labyrinthine fistula. Methods: retrospective review with case series analysis. Results: a labyrinthine fistula was present in 14% of cholesteatoma patients; CT scan was predictive in al cases; the hearing preservation was obtained with both techniques; a recurrence was detected only in one case; postoperative nystagmus incidence was higher in those cases with matrix left in situ and when the size of the fistula was larger than 2 mm. Conclusions: the labyrinthine fistula have to be treated contextually with cholesteatoma removal, both techniques had good postoperative hearing preservation rate. The postoperative vertigo with nystagmus is more frequent in larger fistulas.

To compare cochlear dose and hearing outcomes between intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) in patients with nasopharyngeal carcinoma (NPC). Prospective matched cohorts. Tertiary academic center. A total of 180 newly diagnosed, treatment-naive NPC patients receiving definitive radiotherapy between 2023 and 2025 were enrolled. Patients were 1:1 matched by sex, age, and disease stage, and assigned to IMPT (n = 90) or VMAT (n = 90). Mean cochlear dose was recorded. Audiological evaluations, including pure-tone audiometry (PTA), air-bone gap, and word recognition score, were performed before and after treatment. IMPT delivered significantly lower mean doses to the ipsilateral (47.51 vs 56.82 Gy, P < .001; 95% CI: -14.27 to -4.35) and contralateral cochlea (30.79 vs 45.71 Gy, P < .001; 95% CI: -18.93 to -10.91). Based on each patient's most recent audiometric assessment (median follow-up, 12.1 months; range, 7.5-19.5 months), IMPT demonstrated better average PTA thresholds than VMAT (33.72 vs 42.00 dB; P = .016; 95% CI, -14.91 to -1.65), superior high-frequency hearing at 2 to 8 kHz (37.94 vs 53.82 dB; P < .001; 95% CI, -23.69 to -8.07), lower air-bone gap (5.67 vs 10.62 dB; P < .001; 95% CI, -6.80 to -3.10), and higher word recognition scores (96.67% vs 94.00%; P = .039; 95% CI, 0.14-5.20), with less bone conduction loss at 1 to 4 kHz. IMPT reduces cochlear dose compared to VMAT, resulting in better hearing preservation and suggesting its potential to minimize ototoxicity in NPC patients.

Hearing preservation remains a key goal in the management of vestibular schwannoma. Here, we aimed to evaluate long-term hearing and facial nerve outcomes following hearing preservation surgery for VS. A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed and Embase were searched for studies reporting long-term hearing outcomes after VS resection via the retrosigmoid or middle fossa approach. Studies with at least a 5-year follow-up were included. The primary outcome was long-term serviceable hearing, defined as American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Class A or B. The secondary outcome was long-term preservation of facial nerve function, defined as House-Brackmann Grade I. Of the 1806 studies screened, a total of 8 studies reporting 310 patients with long-term hearing outcomes and 228 patients with facial nerve outcomes were included in the meta-analysis. The pooled proportion of patients with long-term serviceable hearing was 60% (95% CI: 52%-68%), with no significant difference between the retrosigmoid (57%) and middle fossa (60%) approaches (p = 0.63). Facial nerve function was well preserved, with 94% (95% CI: 72%-99%) of patients achieving House-Brackmann Grade I facial nerve function at long-term follow-up. No significant difference was observed between the two surgical approaches in terms of facial nerve function preservation (p = 1.000). In conclusion, long-term preservation of hearing function is feasible in the surgical management of VS and is associated with excellent facial nerve outcomes, with comparable outcomes observed between the retrosigmoid and middle fossa surgical approaches.

TMEM63 is a mechanosensitive transmembrane protein implicated in calcium regulation; however, its specific function in cochlear auditory cells remains undefined. Calcium signaling is essential for cochlear hair cell proliferation, apoptosis, and migration-processes fundamental to hearing preservation and potential regeneration. This research sought to examine TMEM63's regulatory function in proliferation, apoptosis, and migration within HEI-OC1 cochlear hair cell systems, aimed at delineating the involvement of calcium-dependent signaling pathways, particularly the CDC42/AMPK axis. HEI-OC1 cells were subjected to TMEM63 overexpression or knockdown via plasmid transfection or RNA interference. Calcium chelation was performed using BAPTA-AM. Cell proliferation was assessed by CCK-8 screen, apoptosis via Annexin V-fluorescein isothiocyanate/propidium iodide analysis, as well as cellular cycling by flow cytometric evaluation. Wound repair combined with transwell analysis was conducted toward evaluate motility and invasiveness. Intracellular calcium levels were measured using ELISA, and signaling pathway activation was analyzed via Western blot and immunofluorescence. TMEM63 overexpression significantly promoted cell proliferation, enhanced migration, and suppressed apoptosis, while knockdown had the opposite effects. These phenotypes were reversed by BAPTA-AM, indicating a calcium-dependent mechanism. TMEM63 modulated intracellular Ca²⁺ levels and activated CDC42 and CaMKII while suppressing AMPK phosphorylation. Immunofluorescence confirmed consistent changes in CDC42, β-catenin, AMPK, and E-cadherin expression. TMEM63 regulates cochlear hair cell proliferation, apoptosis, and migration through calcium-dependent activation of the CDC42/AMPK signaling pathway. These findings highlight TMEM63 as a potential modulator of cochlear cell function and a novel target for hearing preservation strategies.