The role of DTL in maintaining survival of cochlear hair cell and hearing function.

Abstract Purpose MYO7A is involved in several forms of deafness in humans and mice, and in this study we aimed to investigate if the hearing loss could be reversed after its onset. Methods A knockdown allele of Myo7a in the mouse , Myo7a tm1a , was characterised by recording ABR thresholds at ages from 4 weeks to 6 months old and measuring the amount of hair cell degeneration at 4 weeks old. Scanning electron microscopy was used to assess the condition of stereocilia bundles. A tamoxifen-inducible Flp recombinase was used to activate expression of Myo7a in Myo7a tm1a/tm1a homozygotes at 4 weeks old by excising the transcription disruption cassette in the tm1a allele allowing expression of the Myo7a gene, and ABRs were recorded before and after activation of the gene. Results Myo7a tm1a was found to be a recessive allele causing reduced transcription and early onset profound deafness. Some hair cell loss was found at 4 weeks old, and scanning electron microscopy showed Myo7a tm1a severely affects stereocilia morphology and organisation. Activation of Myo7a expression at 4 weeks old results in very small improvements in ABR thresholds of Myo7a tm1a/tm1a mice at 12 and 18 kHz at 6 and 8 weeks old but there were no responses to sound by 14 weeks old. Conclusions It is likely to be challenging to reverse hearing loss due to very early developmental defects of stereocilia organisation.

Myo7a, a gene mutated in Usher syndrome and nonsyndromic deafness, encodes an unconventional myosin essential for hair cell function. Our previous work revealed that cochlear hair cells express distinct Myo7a isoforms with unique spatial and cell type-specific patterns. The canonical isoform (Myo7a-C) and an additional isoform (Myo7a-N) are co-expressed in outer hair cells (OHCs) but exhibit opposing tonotopic gradients, while inner hair cells primarily express Myo7a-C. These isoforms arise from distinct transcriptional start sites, indicating separate regulatory inputs. Here, we identify an intronic cis-regulatory element, EnhancerA, essential for tonotopically graded Myo7a expression. EnhancerA deletion reduces MYO7A protein levels in a tonotopically varied manner, disrupts hair bundle morphogenesis, alters OHC mechanotransduction, and leads to hair cell degeneration and hearing loss. We further identify SIX2, a tonotopically expressed transcription factor that may interact with EnhancerA to regulate Myo7a-N in OHCs. These findings define a cis-trans regulatory axis critical for isoform-specific Myo7a expression and cochlear function.

Pbx1 overexpression delays cochlear hair cells degeneration in an accelerated aging mouse model.

Sensory hair cells convert sound-induced vibrations into electrical signals through a process called mechanoelectrical transduction (MET). While the protein components of the MET complex are well studied, increasing evidence indicates that MET channel properties are significantly modulated by the surrounding lipid bilayer. The asymmetric distribution of membrane lipids between the inner and outer membrane leaflets is well established to shape membrane mechanics. The recent discovery that the core MET components TMC1 and TMC2 also act as lipid scramblases suggests a direct role for membrane lipid asymmetry in the dynamic shaping of auditory transduction. Because scramblase activity of TMC1/2 disrupts lipid asymmetry, we hypothesized that an opposing flippase may be required to restore and maintain lipid asymmetry. Here, we identify the P4-ATPase ATP8B1 and its chaperone TMEM30B as selectively expressed in outer hair cells (OHCs), enriched in stereocilia, and upregulated following the onset of MET and hearing. Loss of either protein results in elevated auditory brainstem response (ABR) thresholds, phosphatidylserine (PS) externalization, and rapid hair-cell degeneration, demonstrating that lipid homeostasis is crucial for OHC survival. Together, these findings establish ATP8B1 and TMEM30B as key regulators of membrane lipid asymmetry in sensory hair cells and establish TMEM30B as a novel deafness gene.

Age-related hearing loss is characterized by the progressive degeneration of cochlear hair cells and neurons, with mitochondrial dysfunction and impaired mitophagy implicated as molecular mechanisms. Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, plays a critical role in the regulation of mitochondrial quality control and mitophagy. SRT2104, a synthetic SIRT1 activator with improved bioavailability compared to resveratrol, has shown neuroprotective effects in age-related neurodegeneration. However, the role of SIRT1 in auditory cell senescence remains unclear. In this study, we investigated the effects of SRT2104 on cellular senescence and mitophagy in HEI-OC1 auditory cells and organotypic cochlear explants. Senescence was induced using low-dose H₂O₂, and SRT2104 was used as a pre-treatment. SRT2104 significantly enhanced SIRT1 activity, upregulated mitophagy-related proteins (PINK1, Parkin, BNIP3, and LC3-II), and downregulated senescence markers (p53 and p21) in cellular and explant models. β-galactosidase staining confirmed reduced senescence in SRT2104-treated groups. Pre-treatment with SRT2104 preserved mitochondrial function, as indicated by enhanced mitochondrial membrane potential, improved mitochondrial DNA integrity, and increased ATP production. SIRT1 knockdown abolished these protective effects, confirming that SRT2104 mediated its anti-senescence and pro-mitophagy activities via SIRT1. Our findings demonstrated that SRT2104 alleviates premature senescence and promotes mitophagy in auditory cells via SIRT1 activation. The pharmacological activation of SIRT1 may represent a promising therapeutic strategy to counteract age-related degeneration in the auditory system.

Sensorineural hearing loss (SNHL) represents the most common sensory deficit in humans and is increasingly prevalent with aging. Despite diverse etiologies, irreversible degeneration of cochlear hair cells and neurons remains a final pathway for auditory decline. This narrative review synthesizes current preclinical and early clinical evidence on gene- and stem cell-based strategies for congenital and acquired SNHL, highlighting translational progress, delivery innovations, and persisting limitations. A structured literature and registry search (PubMed, Embase, Scopus, Web of Science, ClinicalTrials.gov, EudraCT) was conducted using Boolean combinations of disease-, gene-, vector-, and delivery-related terms. From 140 initial records, 46 eligible studies were included after full-text screening. Data were qualitatively analyzed across two streams-human clinical (gene therapy) and preclinical/experimental (gene editing, RNA-based modulation, stem-cell regeneration). Two independent first-in-human AAV-mediated OTOF replacement trials in children with DFNB9 demonstrated partial restoration of hearing, establishing the first clinical proof-of-concept for cochlear gene therapy. Preclinical studies confirm durable auditory and vestibular rescue using dual-AAV systems, while CRISPR-based editing, antisense oligonucleotides (ASOs), and RNA interference (RNAi) approaches show mechanistic feasibility. Induced pluripotent stem cells (iPSCs) and inner-ear organoids replicate key developmental pathways, supporting modeling and future cellular repair. Delivery precision via the round window, oval window, and microneedle systems remains the major translational bottleneck. Gene- and cell-based approaches are transforming auditory regenerative medicine. Among them, AAV-mediated OTOF replacement has reached clinical validation, whereas CRISPR, ASO/RNAi, and iPSC-derived regeneration continue at advanced preclinical stages. Future success will depend on refining delivery, ensuring long-term safety, and harmonizing ethical and regulatory oversight.

To clarify the ototoxic effects of Castellani solution by using histopathologic and audiological evaluations together, as contradictory results have been presented in the literature. Castellani's solution is effective in treating disorders of the external auditory canal, particularly fungal infections. However, in cases of perforation of the eardrum, it can pass into the middle ear and affect the cochlea or vestibular system adversely. Animals were divided into 4 groups: A: control; B: distilled water; C: Castellani's solution; and D: a solution of 70% isopropyl alcohol and 2% chlorhexidine. After the baseline hearing thresholds were recorded using auditory brainstem responses (ABRs) at 8, 16, 24, and 32 kHz, 0.03mL of the respective substances were injected intratympanically 3 times at 2-day intervals in groups B, C, and D. Group A underwent tympanic membrane perforation using a syringe. ABRs were repeated on days 7 and 21. All animals were then sacrificed and their temporal bones were prepared for a histologic examination of the cochlea. ABRs conducted on days 7 and 21 after the intratympanic intervention revealed total hearing loss in groups C and D, whose hearing levels were significantly lower than those of group A. Histopathologic evaluation revealed cytoplasmic vacuolization and severe atrophy of marginal, basal, and intermediate cells in groups C and D, as well as loss and degeneration of outer hair cells and supporting cells. Due to its potential ototoxic effects and risk of passing into the middle ear, Castellani's solution should be used with extreme caution in cases of tympanic membrane perforation.

Noise-induced hearing loss (NIHL), a common sensory disorder, is traditionally thought to stem primarily from direct damage to sound-sensing hair cells (HCs). Here, we demonstrate that supporting cells (SCs), neighboring cells not previously implicated in NIHL pathogenesis, orchestrate hearing loss and HC degeneration through Gasdermin D (GSDMD) activation. Mechanistically, noise-induced oxidative stress in HCs triggers activation of epidermal growth factor receptor in SCs, leading to extracellular-regulated kinase phosphorylation and caspase-11-dependent cleavage of GSDMD, thereby establishing an HC-to-SC signaling cascade. Furthermore, GSDMD activation in SCs reciprocally exacerbates oxidative injury in HCs, creating a pathogenic positive feedback loop between the two cell types. Our findings uncover a central role for SCs in noise-induced hearing loss and identify GSDMD-mediated intercellular communication as a potential therapeutic target.

Sensorineural hearing loss (SNHL) caused by human cytomegalovirus (HCMV) infection involves alterations in both the central auditory pathways and cochlear structures. Immediate early (IE) proteins are critical for HCMV pathogenicity and have been associated with neurodevelopmental disorders; however, their contribution to HCMV-associated SNHL remains unclear. Here, we generated transgenic mouse models expressing HCMV IE1 and IE2 protein to investigate their effects on auditory function and cochlear pathology. Auditory brainstem response (ABR) measurements revealed that expression of IE2, but not IE1, led to significantly elevated ABR thresholds and impaired auditory processing. IE2-transgenic mice exhibited synaptic loss, hair cell degeneration, and neuronal atrophy in auditory regions. scRNA-seq analysis indicated broad activation of inflammatory pathways and cytokines within the cochlea, along with disruptions in mitochondrial and metabolic pathways, suggesting that IE2 may contribute to hearing loss through mitochondrial impairment and inflammation. Transmission electron microscopy of cochlear tissues showed severe morphological abnormalities and a marked reduction in mitochondrial number in spiral ganglion neurons (SGNs). Further mechanistic investigation demonstrated that IE2 interacts with TSC2, leading to hyperactivation of mTOR signaling, metabolic dysregulation, and mitochondrial dysfunction. Importantly, administration of mTOR inhibitors substantially alleviated IE2-induced auditory deficits, hair cell degeneration, and neuronal atrophy. These findings identify IE2 through TSC2–mTOR-mediated mitochondrial dysfunction, metabolic reprogramming, and neuroinflammation leading to SNHL. Our study reveals a previously unrecognized mechanism linking IE2 protein expression to auditory neurodegeneration and suggests mTOR modulation as a potential therapeutic strategy for congenital HCMV infection and associated hearing loss.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12974-025-03646-6.

Damage to inner hair cells (IHCs) is a leading cause of hearing loss, typically initiating at the base region of the basilar membrane. However, the mechanisms and preventative strategies for IHC damage remain to be elucidated. This study revealed that IHCs in the low-frequency region exhibit a significantly faster calcium clearance rate than high-frequency IHCs. This difference is associated with different PMCA1 expression. We then generated an IHC-specific Pmca1 knockout mouse model (Pmca1 CKO) exhibiting profound hearing loss and IHC death. Using single-cell RNA-seq analysis, we found that the differentially expressed genes (DEGs) were related to tetrahydrofolate biosynthesis, DNA damage, and DNA repair dysfunction. We therefore treated Pmca1 CKO mice with folic acid and found that it protected IHCs by reducing γ-H2A.X levels. In addition, we found that folic acid protected IHCs from noise-induced damage. Overall, our findings suggest that disrupted calcium homeostasis plays a role in IHC damage and that folic acid may be a promising therapeutic agent for protecting hair cells.

Bilateral vestibular dysfunction disrupts balance and spatial orientation, yet mechanisms of injury and compensation remain incompletely defined. We established a mouse model of bilateral acute inner-ear (labyrinthine) injury with vestibular involvement by sequentially incising the round and oval windows, and evaluate auditory brainstem responses (ABR), vestibular sensory-evoked potentials (VsEP), behavior, and histology across postoperative days 1-28. Threshold elevations and behavioral impairment peaked on day 3, with hair-cell degeneration most prominent early and partial morphological recovery by day 28. These findings delineate the acute injury phase and early stabilization, providing a platform to study vestibular repair and functional recovery.

HighlightsNeuromast cells in the Astyanax mexicanus lateral line system are sensitive to neomycin (Aminoglycosides).Neuromast cells disappeared within 24 h of neomycin treatment and returned to baseline levels by 72 h post-exposure.Gene expression levels of fgf1 and axin2 showed a slight increase during neuromast cell regeneration following neomycin exposure, whereas sox2 expression remained relatively unchanged.Neuromast cells are specialized mechanosensory receptor cells embedded within the lateral line system of aquatic vertebrates, enabling the detection of water movement and vibration that are essential for navigation, prey capture, and predator avoidance. These cells share common evolutionary and functional homology with mammalian inner ear hair cells, both of which rely on stereocilia-mediated mechano-transduction and ion channel activation to convert mechanical stimuli into neural signals. Unlike their mammalian counterparts, neuromast hair cells possess a regenerative capacity following damage, making the lateral line system a unique model for studying hair cell regeneration and sensory restoration. This study examines the potential of the Mexican tetra (Astyanax mexicanus) as a novel model organism for investigating ototoxicity and regeneration of neurosensory hair cells. Here, we explore the cranial and trunk lateral line neuromasts, including deep canal neuromast cells located in facial bones, such as the mandible and circumorbital bones. In the present study, juvenile surface-dwelling Mexican tetra were exposed to a 500 µM neomycin for 4 h to induce targeted hair cell damage. The samples were collected at 4-, 12-, 24-, and 72 h post-exposure. Furthermore, neuromast cell viability was assessed using [2-(4-(Dimethylamino) styryl)-N-ethylpyridinium iodide] (DASPEI). Gene expression analysis revealed a modest increase in Fibroblast Growth Factor 1 (fgf1) and Axis Inhibition Protein 2 (axin2) expression following treatment; however, these changes were not statistically significant. The SRY-box transcription factor 2 (sox2) remains constant throughout the exposure and recovery period. These findings highlighted the regenerative dynamics of neuromast cells in Mexican tetra. This work lays the foundation for future therapeutic strategies targeting human sensory deficits, particularly those involving inner ear hair cell degeneration.

Distribution of macrophages in the cochlea following radiation-induced sensorineural hearing loss.

Vesicular glutamate transporter 3 (VGLUT3) is prominently expressed in the inner hair cells of the cochlea, playing a vital role in auditory signal transmission to the brain. Previous studies have shown that Vglut3 gene knockout in mice causes severe sensorineural hearing loss without affecting hair cell integrity. However, the cochlear structure of the aged Vglut3KO remains inadequately explored. In this study, we analyzed the cochlear structure of aged Vglut3KO mice, revealing significant degeneration of inner hair cells, synapses, and stereocilia. To explore the potential of gene therapy to restore cochlear structure, we employed AAV8 vectors to express Vglut3 in the cochleae of 5-week-old Vglut3KO mice. Twenty-seven weeks post-injection, we conducted a series of experiments to evaluate the efficacy of our gene therapy approach. Auditory brainstem response (ABR) testing demonstrated restoration of auditory function following gene therapy. Immunohistochemical staining and scanning electron microscopy (SEM) analysis revealed substantial recovery of inner hair cells and stereocilia post-injection. Our findings provide important insights into the development of novel therapeutic strategies for age-related hearing loss.

Sensorineural hearing loss (SNHL) is characterized by cochlear inflammation, macrophage activation, and degeneration of hair cells, synapses, and neurons. Macrophage-mediated inflammation in the damaged cochlea is regulated via CX3CR1-CX3CL1 signaling, where the fractalkine ligand CX3CL1 serves as a chemotactic and calming signal for macrophage activation. Furthermore, disrupted CX3CR1-CX3CL1 signaling in CX3CR1-KO and CX3CL1-KO mice leads to reduced macrophage numbers, exacerbated inflammation, and loss of hair cells, ribbon synapses, and neurons in the damaged cochlea. Notably, ~ 25% of the human population carries single-nucleotide polymorphisms (SNPs) in the CX3CR1 gene, CX3CR1I249/M280, which results in a receptor with lower binding affinity for CX3CL1, while most individuals carry the common wild-type CX3CR1V249/T280 allele. Although these polymorphisms are associated with various CNS neurodegenerative disorders, their impact on SNHL, cochlear degeneration and the macrophage response remains largely unknown. Here, we used a humanized mouse model expressing human CX3CR1 SNPs in lieu of its murine counterpart to investigate the effects of I249/M280 polymorphisms on cochlear function and structure following noise trauma. Young CX3CR1 WT, CX3CR1 KO, and human CX3CR1I249/M280 mice of both sexes were exposed to a noise level of 93 decibel sound pressure for 2h at an octave band (8-16kHz). Cochlear function was assessed prior to exposure and at 1day and 2weeks postexposure. Also, the densities of inner and outer hair cells, ribbon synapses, and macrophages in Rosenthal's canal were examined after two weeks of exposure and compared among the three genotypes. We found that at 2weeks postexposure, hearing thresholds were elevated and input‒output function was impaired in hCX3CR1I249/M280 and CX3CR1 KO, whereas mice carrying WT alleles showed functional recovery. A significant synaptic loss (~ 30%) in hCX3CR1I249/M280 and CX3CR1 KO mice was observed relative to that in WT, which exhibited synaptic repair. hCX3CR1I249/M280 resulted in a ~ 17% loss of outer hair cells, which correlated with reduced otoacoustic emissions in the basal cochlear region. Noise led to increased macrophage numbers in the spiral ganglion and lateral wall of the WT; however, this response was attenuated in the CX3CR1 KO and hCX3CR1I249/M280 strains. Additionally, macrophages from CX3CR1 KO and hCX3CR1I249/M280 mice presented altered morphology, increased CD68 expression, and inflammation. Compared with those of mice carrying the CX3CR1 WT or KO allele, young hCX3CR1I249/M280 mice fostered under ambient noise presented early elevations in hearing thresholds at basal frequencies. Together, these findings reveal that human CX3CR1 variant-mediated macrophage dysregulation strongly correlates with worsening of hearing loss and cochlear degeneration after noise trauma. Our work proposes a novel immune-related genetic polymorphism that may aid in the identification of individuals with increased vulnerability to SNHL.

Background and PurposeCisplatin is a widely used chemotherapy drug for the treatment of solid tumours, but its clinical benefit is often limited by ototoxicity, leading to irreversible sensorineural hearing loss. However, there is a lack of effective strategies to prevent hearing loss caused by cisplatin in adults, while sodium thiosulfate is approved by the Food and Drug Administration in the United States for only use at the pediatric level. Sarsasapogenin, a natural compound of the Anemarrhena asphodelides, has antioxidant and neuroprotective properties, which suggest that it may attenuate the ototoxicity induced by cisplatin. The aim of this study is to evaluate the otoprotective effects of sarsasapogenin and its underlying mechanism as a potential therapeutic intervention for the prevention of ototoxicity induced by cisplatin.MethodsCell viability was assessed by CCK-8 and cell apoptosis was assessed by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial dysfunction were quantified by immunofluorescence. In addition, expression of the molecules involved in apoptosis and ferroptosis was analyzed by qRT-PCR and Western blot. In vivo auditory function was evaluated by auditory brainstem response testing, and the survival of hair cells in the cochlea was quantified by immunolabeling with myosin-VIIa.ResultsSarsasapogenin significantly alleviated cisplatin-induced oxidative stress and restored mitochondrial function in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. Furthermore, sarsasapogenin effectively protected against cisplatin-induced sensorineural hearing loss and hair cell degeneration in vivo. Mechanistically, the protective effects of sarsasapogenin were primarily mediated through the inhibition of apoptosis and ferroptosis, both in vitro and in vivo.ConclusionThis study provides compelling evidence for the otoprotective effects of sarsasapogenin, suggesting its potential as a therapeutic intervention to prevent cisplatin-induced hearing loss.

Sensorineural hearing loss is characterized by irreversible hair cell (HC) degeneration. Ferroptosis, which is marked by the accumulation of reactive oxygen species and elevated levels of lipid peroxidation products, has been shown to contribute to drug-mediated auditory impairment. This study aimed to elucidate the role of mixed-lineage leukemia 1 (MLL1) in HC survival in the auditory system. The HEI-OC1 auditory cell line and postnatal cochlear explants were evaluated using MM-102, a specific MLL1 histone methyltransferase inhibitor. Western blot, quantitative polymerase chain reaction, electron microscopy, and immunofluorescence were used to elucidate the role of MLL1 in regulating ferroptosis in HC injury. RNA sequencing (RNA-seq) was used to analyze the molecular mechanisms of MLL1 intervention in HC injury from an epigenetic perspective. Our findings demonstrated that immunofluorescence staining revealed crucial role of MM-102 in promoting intracellular accumulation of lipid peroxides and ferrous ions. Subsequent analysis showed MLL1 downregulation-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress, with transmission electron microscopy imaging confirming ultrastructural alterations in mitochondria and ER. Mechanistic investigations identified the PERK-eIF2α-Atf4-Chop signaling axis as the regulatory pathway, evidenced by Western blot quantification of phosphorylated PERK (p-PERK), Atf4, and Chop levels. RNA-seq analysis revealed 741 differentially expressed genes (335 upregulated, and 406 downregulated). KEGG pathway analysis specifically highlighted significant enrichment of the PI3K/Akt-Lrp1 pathway, with corresponding activation patterns of phospho (p)-Akt and Lrp1 confirmed through Western blot analysis. MLL1 downregulation initiates ferroptosis in cochlear HCs. This process is intrinsically associated with the activation of mitochondrial dysfunction and ER stress. The study highlights the importance of MLL1 in HC survival, suggesting its potential as a therapeutic target for treating hearing loss.

Cochlear aging causes substantial hearing impairment in older adults, yet primate-specific mechanisms remain poorly characterized. Our comprehensive analysis combining single-cell and histopathological profiling in aging Macaca fascicularis demonstrates progressive cochlear degeneration featuring accelerated sensory hair cell loss, senescent spiral ganglion neurons with elevated neuroinflammation, and marked stria vascularis atrophy. We discovered that downregulation of transmembrane transport proteins, particularly SLC35F1, serves as a critical biomarker of hair cell aging. Functional validation through Slc35f1 knockdown in adult mice successfully recapitulated key aspects of age-related hearing loss, including hair cell degeneration and auditory function decline. Notably, we showed that long-term metformin administration at clinically relevant doses effectively delays cochlear aging in primates. These findings provide fundamental insights into the cellular and molecular basis of primate cochlear aging while establishing a foundation for developing targeted interventions against age-related hearing loss.

BackgroundA novel in-frame insertion variant in the B-Cell Receptor-Associated Protein 31 (BCAP31) gene, which encodes a crucial ER membrane protein involved in the quality control and transport of transmembrane proteins, as well as in ER-mitochondria apoptotic signaling, was determined in a family demonstrating X-linked, recessive, nonsyndromic auditory neuropathy spectrum disorder (ANSD).MethodsExome sequencing analysiswas followed by bioinformatics analysis to identify the cause of hearing loss in a family whose pedigree indicated an X-linked recessive mode of inheritance. Immunohistochemistry was performed to locate Bcap31 in the mouse cochlea. Mitochondrial function was evaluated by measuring intracellular ATP, ROS and mitochondrial membrane potential in control and patient-derived lymphoblastoid cells (LCLs) before and after the administration of mitochondria isolated from human umbilical cord mesenchymal stem cells (UC-MSCs).ResultsANSD observed in our study is characterized by initial inner hair cell damage, followed by accelerated degeneration of cochlear outer hair cells. Functional studies of patient-derived LCLs revealed mitochondrial dysfunction, evidenced by increased ROS, reduced ATP levels, and decreased mitochondrial membrane potential compared with normal LCLs. Further, these cells demonstrated heightened sensitivity to cisplatin-induced apoptosis, as indicated by the increased proapoptotic gene expression. Notably, the administration of mitochondria isolated from umbilical cord mesenchymal stem cells significantly restored mitochondrial dysfunction and alleviated cisplatin-induced cytotoxicity in the patient-derived cells.ConclusionsThese results indicate BCAP31 dysfunction as a potential cause of transient ANSD, progressing to sensorineural hearing loss through mitochondrial impairment. Furthermore, they highlighted the therapeutic potential of allogenic mitochondrial transplantation as a novel strategy for treating hearing loss with an underlying component of mitochondrial dysfunction. This study contributes to the understanding of BCAP31’s role in auditory neuropathy and mitochondrial health.Graphical