Epididymal protease inhibitor (EPPIN)

Epididymal protease inhibitor (EPPIN) is a secreted, cysteine-rich protein found on the surface of human sperm, encoded by the SPINLW1 gene on chromosome 20q12-13.2[2][3][6]. EPPIN contains both a Kunitz-type and a WAP (whey acidic protein) four-disulfide core (WFDC) domain and is part of a gene family implicated in protease inhibition and host defense[1][3][6]. During ejaculation, EPPIN binds semenogelin-1 (SEMG1), temporarily inhibiting sperm motility; subsequent cleavage of SEMG1 by prostate-specific antigen (PSA/KLK3) restores sperm motility in the female tract[1][2][6]. EPPIN is essential for male fertility, as its disruption by anti-EPPIN antibodies or small molecules (such as EP012 and EP055) impairs sperm motility and provides reversible male contraception in preclinical models[1][2]. EPPIN also provides antimicrobial protection to sperm in the ejaculate and is under investigation both as a therapeutic contraceptive target and as a gene implicated in some infertility cases[2][6][1].

Other names

EppinSPINLW1WAP7WFDC7CT71Epididymal peptidase inhibitorCancer/testis antigen 71Cancer/testis antigen 72Protease inhibitor WAP7Serine peptidase inhibitor-like with Kunitz and WAP domains 1WAP four-disulfide core domain protein 7Epididymis secretory sperm binding proteindJ461P17.2

Inhibition of EPPIN-SEMG1 binding (and thus sperm motility); Spermiostatic effect via modulation of sperm surface protein interactions