PRSS37 (serine protease 37) is a sperm-specific serine protease essential for male fertility. Expressed predominantly in testis during spermiogenesis, PRSS37 localizes to the acrosome region of mature sperm and plays a critical role in regulating the proacrosin/acrosin system activation 1. The protein is involved in controlling proteolysis of acrosomal proteins, including ADAM2, which is necessary for sperm functional competence during fertilization 1. PRSS37-deficient mice are sterile despite normal spermatogenesis, morphology, and motility, and human PRSS37 can rescue this phenotype, indicating functional conservation 2. Low sperm PRSS37 levels are associated with unexplained male infertility (UMI) in men, with affected sperm showing premature acrosin activation and abnormal proteolysis 1. Critically, reduced PRSS37 impairs in vivo fertilization capability but not in vitro outcomes, suggesting its role in sperm-zona pellucida interaction 1. PRSS37 serves as a potential molecular biomarker for evaluating sperm fertilization potential and represents a promising non-hormonal contraceptive target 12. Proteomics studies identify PRSS37 among key candidate proteins for monitoring sperm quality in male infertility diagnosis 345.