CRISP1 (cysteine-rich secretory protein 1) is a multifunctional epididymal protein essential for male fertility through its roles in sperm maturation and gamete interaction. The protein is expressed in the epididymis and associates with sperm during transit, existing in two populations: a loosely bound fraction released during capacitation acting as a decapacitating factor, and a firmly associated fraction participating in fertilization 1. CRISP1 localizes to the dorsal region of capacitated sperm and migrates to the equatorial segment during the acrosome reaction, positioning it for sperm-zona pellucida (ZP) interaction 1. Mechanistically, CRISP1 mediates sperm binding to the ZP through its conserved Signature 2 motif, which interacts with complementary egg surface sites to promote gamete fusion 2. The protein also undergoes zinc-dependent oligomerization via its CAP domain metal-binding site, potentially facilitating functional protein complex formation during sperm condensation 3. CRISP1 knockout sperm exhibit impaired protein tyrosine phosphorylation and reduced fertilization capacity 1. Notably, CRISP1 and its homolog CRISP4 show functional redundancy; single knockouts remain fertile, but double CRISP1/CRISP4 knockout mice demonstrate reduced fertility, abnormal epididymal epithelium differentiation, and altered luminal pH 4. Additionally, CRISP1 functions as a hair shaft structural protein, with dysregulated expression potentially predisposing to follicular dystrophy 5.