WFDC9 is a reproductive tract-specific gene encoding a member of the whey acidic protein four-disulfide core domain family. It functions as a serine-type endopeptidase inhibitor with roles in innate immune response and antibacterial humoral defense 1. In the male reproductive system, WFDC9 is expressed in the epididymis and is present in epididymosomes, extracellular vesicles that deliver cargo between reproductive tissues 2. Functionally, WFDC9 is critical for male fertility: mice with targeted deletion of Wfdc9 (as part of a five-gene knockout cluster) maintain normal spermatogenesis and sperm counts but exhibit severe infertility due to defects in sperm motility and increased sperm death 1. WFDC9 expression is region-specific within the male reproductive tract and changes with reproductive aging 3. Clinically, WFDC9 mRNA levels in seminal plasma can serve as an epididymis-specific biomarker, though measurements are sensitive to scrotal heat stress and may be relevant for diagnosing male infertility 4. These findings suggest WFDC9 as a potential target for understanding male reproductive pathology and developing diagnostic tools for fertility assessment.