Purpose Aminoacylase 1 (ACY1) catalyzes the hydrolysis reaction during protein degradation. N-acetylamino acids are accumulated in the urine in Aminoacylase 1 deficiency (ACY1D). This study attempts to evaluate the potential of ACY1 as a biomarker for schizophrenia and predict genetic vulnerability in the high-risk population. Material and methods Seventy patients with schizophrenia, twenty-five of which have newly diagnosed, forty-nine unaffected siblings of patients, and fifty-six healthy controls were included in the study. The ELISA method was used to measure serum ACY1. The Positive and Negative Syndrome Scale (PANSS) and The Clinical Global Impression – Severity scale (CGI-S) were used to analyze the severity of the symptoms. Data were analysed statistically by non-parametric tests. Results The finding of the study indicated that the serum levels of ACY1 in patients and siblings were lower compared to healthy controls (p < 0.001 and p = 0.023). There was no statistically significant difference between patients and siblings (p = 0.067). The duration of disease, PANSS total scores, and CGI-S scores did not have a significant association with the ACY1 levels in the patient group (p > 0.005). ACY1 levels among the drug-using patient group and the newly diagnosed patient group showed no notable difference (respectively, p = 0.120 and p = 0.843). Conclusion This study is the first to evaluate the serum ACY1 levels in patients with schizophrenia. The result of the study provides us insight regarding the first hints that ACY1 might be a potential biomarker. Being aware of the molecule will pave the way for further explorations in the field.