SPRR2A (small proline-rich protein 2A) serves as a multifunctional protein with distinct roles in antimicrobial defense and tissue remodeling. As an antimicrobial protein, SPRR2A is expressed in Paneth cells and goblet cells where it selectively kills Gram-positive bacteria by binding to negatively charged bacterial membrane lipids such as phosphatidic acid, phosphatidylserine, cardiolipin, and phosphatidylinositol phosphates, leading to membrane permeabilization and bacterial death 1. This antimicrobial activity is induced by type 2 cytokines during helminth infections and protects against helminth-induced bacterial invasion of intestinal tissue 1. Beyond its antimicrobial function, SPRR2A plays important roles in epithelial remodeling and wound healing. In chr1 rhinosinusitis with nasal polyps, SPRR2A promotes eosinophilic inflammation and tissue remodeling through upregulation of SAA2, contributing to epithelial-mesenchymal transition and barrier dysfunction 2. In cholangiocarcinoma, SPRR2A complexes with transcription factors to suppress miR-200c/141, promoting epithelial-mesenchymal transition that increases local tumor invasiveness while paradoxically preventing metastasis 34. Additionally, serum SPRR2A levels serve as a diagnostic biomarker for gastric cancer, correlating with lymph node metastasis and tumor stage 5.