WFDC13 (WAP four-disulfide core domain 13) is a putative serine-type endopeptidase inhibitor with roles in reproductive function and innate immunity. Located on chromosome 20, WFDC13 is part of a highly conserved syntenic gene cluster of 11 reproductive tract-specific genes that have maintained functional significance across 96 million years of mammalian evolution 1. CRISPR/Cas9 knockout studies demonstrate that WFDC13 contributes to male fertility, with deletion of WFDC13 (alongside Wfdc9, Wfdc10, and Wfdc11) resulting in infertility due to defects in sperm motility and increased sperm death, despite normal spermatogenesis 1. WFDC13 is region-specifically expressed in the male reproductive tract, with expression identified in the epididymis and showing age-related changes during reproductive aging 2. During inflammatory conditions, WFDC13 expression is dynamically regulated by lipopolysaccharide-induced epididymitis through NF-κB-dependent mechanisms, suggesting roles in innate immune responses 3. Beyond reproduction, WFDC13 expression is regulated in colon cancer through the PAN3-AS1/miR-423-5p/WFDC13 axis and is associated with altered immune microenvironments and immunotherapy efficacy 4. These findings indicate WFDC13 functions in both reproductive physiology and immune homeostasis across different tissues.