Epididymal protease inhibitor (EPPIN) (EPPIN)

Epididymal protease inhibitor (EPPIN) is a cysteine-rich protein essential for male fertility, primarily expressed in the testis and epididymis and localized on the surface of ejaculated spermatozoa (UniProt: O95925). It belongs to the Whey Acidic Protein (WAP) family and functions as a serine protease inhibitor that regulates sperm motility by interacting with Semenogelin 1 (SEMG1) in the seminal coagulum (Silva et al., 2012). This interaction protects sperm from premature capacitation and provides antimicrobial defense within the male reproductive tract. EPPIN is a high-priority target for non-hormonal male contraception; blocking its function with small molecules like EP055 or through immunocontraception leads to a significant and reversible reduction in sperm progressive motility (O'Rand et al., 2018). Because its expression is highly tissue-specific to the male reproductive system, it offers a promising pathway for developing contraceptives with minimal systemic side effects.

Other names

SPINLW1WAP four-disulfide core domain protein 7WFDC7Epididymal secretory protein 71WAP7

Small molecule binding to the EPPIN surface or antibody-mediated neutralization blocks the interaction between EPPIN and Semenogelin 1 (SEMG1), or directly inhibits EPPIN's regulatory role in sperm physiology, resulting in the rapid and reversible loss of progressive sperm motility (O'Rand et al., 2018; Silva et al., 2012).