PRSS1 encodes cationic trypsinogen, a serine protease with endopeptidase activity against multiple synthetic substrates, with the single-chain form demonstrating greater activity than the two-chain form 1. As a secreted enzyme, PRSS1 functions in protein digestion and extracellular matrix proteolysis within the pancreas 2. Pathogenic PRSS1 variants cause hereditary pancreatitis through gain-of-function mechanisms. Most high-penetrance variants increase intrapancreatic trypsin activity by enhancing trypsinogen autoactivation and/or inhibiting chymotrypsin C-mediated degradation, while others induce trypsinogen misfolding causing endoplasmic reticulum stress 1. The R122H mutation exemplifies this, promoting pancreatic inflammation and exacerbating acute and chr7 pancreatitis induced by multiple triggers including lipopolysaccharide, ethanol, and high-fat diet 3. Clinically, approximately 1% of chr7 pancreatitis patients carry PRSS1 mutations associated with hereditary pancreatitis 2. PRSS1 variants are classified as disease-causing genes (distinct from disease-predisposing genes like CFTR), and mutation-positive patients show significantly earlier disease onset and faster progression to pancreatic complications including diabetes and steatorrhea 4. Beyond pancreatic disease, emerging evidence suggests PRSS1 differential expression may serve as a biomarker in gestational diabetes mellitus 5. Additionally, PRSS1 has been identified as a regulatory protein in innate immunity, where L-alanine-mediated PRSS1 inhibition affects NF-ΞΊB pathway activation relevant to antimicrobial defense 6.
No tissue expression data available for this gene.