WFDC6 (WAP four-disulfide core domain 6) encodes a serine protease inhibitor located within a conserved gene cluster on chromosome 20 that plays critical roles in male reproductive function 1. As part of a syntenic cluster of 11 closely related reproductive tract-specific genes highly conserved across mammals, WFDC6 contributes to spermatogenesis; males with deletions encompassing WFDC6 among other cluster genes exhibit sterility due to arrest in spermatogenesis at the round spermatid stage 1. The WFDC locus genes function in both immunity and fertility, with WFDC6 displaying signatures of strong selective constraints across primate evolution, suggesting adaptive importance for reproductive immunity 2. WFDC6 shows evidence of population-specific evolutionary selection patterns, with variants potentially affecting gene regulation and expression levels 3. Clinically, WFDC6 expression levels are associated with overall survival outcomes in late-onset ovarian serous cystadenocarcinoma patients, indicating potential relevance to cancer prognosis 4. These findings suggest WFDC6 is essential for male fertility and reproductive tract immune function, with implications for understanding male infertility etiology and identifying therapeutic targets for contraception and cancer management 1.