CELA3B (chymotrypsin-like elastase 3B) is a serine-type endopeptidase with alanine specificity expressed primarily in pancreatic acinar cells 1. It functions as an efficient protease with minimal elastolytic activity [UniProt annotation], and is a major component of pancreatic digestive secretions detected in fecal elastase clinical assays 2. Mechanistically, CELA3B is secreted as an inactive proenzyme and forms stable complexes with procarboxypeptidases A1 and A2, facilitating coordinated proteolysis 3. In addition to digestive function, CELA3B acts as a serine protease that activates protease-activated receptor 2 (PAR2) on sensory neurons, contributing to pain signaling pathways 4. CLEA3B variants are associated with chr1 pancreatitis (CP) risk. Loss-of-function variants, including the splice-site variant c.129+1G>A, increase CP susceptibility (OR=4.4-5.1) 5, while gain-of-function variants p.Arg90Cys and p.Arg90Leu also predispose to CP 6. Additionally, CELA3B is upregulated in type 2 diabetes, where aberrant expression within pancreatic islets reduces β-cell viability 7. Clinically, CELA3B immunohistochemistry is a highly specific (99.9%) pancreatic biomarker for acinar cell carcinoma diagnosis 1, and elevated plasma EV levels of CELA3B show promise as a biomarker for diabetic retinopathy progression 8.