EPPIN (epididymal peptidase inhibitor) is a cysteine-rich serine protease inhibitor essential for male fertility, encoded on human chromosome 20-13.2 1. The 133-amino acid protein contains both Kunitz-type and WAP-type consensus sequences and is secreted by Sertoli cells and epididymal epithelial cells, where it localizes to spermatozoa as part of a protein complex with lactotransferrin and clusterin 2. EPPIN's primary functions include modulating prostate-specific antigen (PSA) activity during semenogelin hydrolysis, providing antimicrobial protection to ejaculated sperm, and binding semenogelin to inhibit sperm motility 1. During ejaculation, semenogelin binding to EPPIN initiates a cascade enabling progressive sperm motility as PSA enzymatically processes the coagulum 2. EPPIN expression occurs in spermatogonia and early spermatocytes, with protein localization concentrated on the sperm tail 3. Immunization studies in male primates demonstrate EPPIN's essentiality—anti-EPPIN antibodies induce complete, reversible contraception 1. This makes EPPIN a validated target for non-hormonal male contraceptive development, with researchers developing compounds that inhibit EPPIN-semenogelin interactions to block sperm motility 4. Clinical relevance includes potential diagnostic applications for male infertility and vaccine-based contraceptives 5.