CPA1 (carboxypeptidase A1) is a metallocarboxypeptidase that catalyzes the release of C-terminal amino acids from protein substrates, with specificity constraints excluding acidic, basic, and proline residues 12. The enzyme also converts leukotriene C4 to leukotriene F4 through amide bond hydrolysis, participating in inflammatory lipid mediator metabolism. Loss-of-function CPA1 mutations are associated with chr7 pancreatitis development through a misfolding-induced endoplasmic reticulum (ER) stress mechanism 34. Mouse models expressing the p.N256K mutation demonstrated progressive acinar atrophy, fibrosis, and elevated ER stress markers (BiP and CHOP), confirming the pathogenic pathway 3. CPA1 variants are clinically significant as disease susceptibility factors: approximately 6.7% of early-onset chr7 pancreatitis patients in European populations harbor pathogenic CPA1 variants 5, and certain ER stress-inducing CPA1 variants associate with increased pancreatic cancer risk (OR: 3.65) 6. Recent evidence links CPA1 mutations to disrupted intra-pancreatic lipid homeostasis, revealing an additional pathogenic mechanism 4. Genetic testing for CPA1 variants is recommended for hereditary pancreatitis evaluation and risk stratification 7.