Serine peptidase inhibitor Kazal type 4 (SPINK4)

Serine peptidase inhibitor Kazal type 4 (SPINK4) is a secreted serine protease inhibitor primarily expressed by goblet cells in the gastrointestinal tract. It modulates the defense against proteolytic degradation in mucosal tissues, regulates epithelial regeneration, and maintains the integrity of intestinal barriers by acting through the EGFR and related signaling pathways. SPINK4 is dynamically regulated in diseases such as IBD and colorectal cancer, where it serves both as a noninvasive biomarker and as a modulator of disease progression and therapeutic response. High SPINK4 immunoexpression correlates with poor outcomes in rectal cancer, and recombinant SPINK4 provides therapeutic benefit in preclinical colitis models by promoting goblet cell differentiation and mucosal recovery. Its key molecular features include a Kazal-type inhibitory domain and secretion into the extracellular space.

Other names

PEC-60HEL136PEC60Peptide PEC-60 homologMGC133107epididymis luminal protein 136gastrointestinal peptide

Recombinant SPINK4: Supplementation restores goblet cell number, enhances mucosal differentiation, and reduces inflammation via EGFR signaling. It modulates the EGFR pathway, leading to activation of downstream Ras-MAPK and AKT signaling in intestinal epithelial cells. It also impacts Wnt/β-catenin and Hippo pathways in mucosal repair.