Cystatin-related epididymal spermatogenic protein (CST8)

Cystatin-related epididymal spermatogenic protein (CST8) is a reproductive tract-specific member of the cystatin superfamily, exhibiting both structural and regulatory functions[1][2][5]. Unlike classical cystatins, CST8 (CRES) acts as a cross-class inhibitor by selectively blocking the serine protease prohormone convertase 2 (PC2) at nanomolar concentrations[1]. During spermatogenesis, CST8 is synthesized by elongating spermatids, secreted by the caput epididymis, and becomes associated with spermatozoa, particularly in the outer dense fibers of sperm tails and the equatorial segment of sperm heads[1][4]. Deletion of CST8 in mice impairs sperm capacitation and alters epididymal architecture, highlighting its essential role in fertility[1][3]. CST8 also displays innate antimicrobial activity, attributed to its N-terminal region, which can permeabilize bacterial membranes and inhibit macromolecular synthesis[1]. In addition, CST8 is expressed in the neuroendocrine system (anterior pituitary), where its synthesis is hormonally regulated, implicating it in broader reproductive regulation[1]. Its expression and biological effects are tissue-specific, with strong localization to the male reproductive tract[1][2][4][5].

Other names

CRESCTES5Cystatin-8Cystatin-related epididymal spermatogenic proteinCystatin-related epididymal specificEpididymis secretory sperm binding protein