Signal peptide peptidase-like 2C (SPPL2C)

Signal peptide peptidase-like 2C (SPPL2C) is an intramembrane aspartyl protease of the SPP/SPPL family, categorized by conserved 'YD' and 'GxGD' active site motifs located within transmembrane domains[5][2]. SPPL2C is primarily and highly expressed in the testes—particularly in spermatids—of mouse and human, where it supports male germ cell differentiation, vesicular trafficking, acrosome formation, and Ca²⁺ regulation through proteolytic cleavage of specific substrates such as phospholamban and SNARE proteins[2][3][6][7]. While other family members such as SPPL2A and SPPL2B have known immunological or pathophysiological roles, SPPL2C’s loss in mice leads to partial defects in spermatid maturation and reduced sperm motility, but maintains overall fertility. No direct human disease associations or connections to drug targeting, biomarkers, or safety concerns have been established as of current knowledge[2][4].

Other names

SPPL2CIMP5SPP-like 2CSPPL2cIMP-5Intramembrane protease 5

Proteolytic cleavage of transmembrane or tail-anchored proteins (e.g., SNARE proteins, phospholamban/PLN)