WFDC10A (WAP four-disulfide core domain 10A) is a reproductive tract-specific gene encoding a serine-type endopeptidase inhibitor with antimicrobial properties. It is part of a highly conserved WFDC gene cluster on chromosome 20, with orthologous genes preserved across mammalian species over 96 million years of evolution 1. Primary Function and Mechanism: WFDC10A contributes to male reproductive function as part of the WFDC gene cluster. While WFDC10A-specific knockout studies were not individually detailed, cluster deletion studies demonstrated that WFDC genes (including WFDC9, WFDC10, WFDC11, WFDC13) regulate sperm motility and viability; their deletion caused infertility despite normal spermatogenesis 1. WFDC10A is highly expressed in the epididymal caput region, where it exhibits antibacterial activity 2. A derived peptide from WFDC10A inhibits gram-negative bacterial growth and permeabilizes bacterial cell membranes without affecting mammalian cells, suggesting a role in innate immune defense of the male reproductive tract 2. Disease Relevance: WFDC10A functions in the first-line immune defense against microbial infections in the epididymis, protecting sperm 2. Emerging evidence suggests tumor-suppressor activity; mebendazole treatment significantly upregulated WFDC10A expression in aggressive breast cancer cells (>40-fold increase, p<0.001) 3, indicating potential involvement in cancer regulation. Clinical Significance: WFDC10A mutations may contribute to male infertility pathogenesis, with implications for clinical diagnosis and potential contraceptive development 1.