CTRB1 encodes chymotrypsinogen B1, a serine-type endopeptidase precursor secreted into the extracellular pancreatic environment 1. Upon activation to chymotrypsin, CTRB1 protects against pancreatitis by degrading intrapancreatic trypsin; CTRB1-deficient mice develop significantly more severe cerulein-induced pancreatitis with elevated trypsin activity 1. A common variant near CTRB1 (rs8056814) is protective against age-related macular degeneration, reducing disease risk (OR=0.71) 2. In Type 1 diabetes, CTRB1 variants colocalize with GWAS signals and show causal involvement in disease pathogenesis 3. Conversely, a CTRB2 exon 6 deletion variant (orthologous to CTRB1 in mice) increases pancreatic cancer risk through ER stress and inflammatory pathway activation, though heterozygous carriers show intermediate phenotypes 4. CTRB1 variants show limited association with GLP-1 receptor agonist response in type 2 diabetes treatment 56. CTRB1 expression is ectopically upregulated in autoimmune gastritis-affected gastric mucosa alongside intestinal and pancreatic trans-differentiation markers 7. These findings establish CTRB1 as a multifunctional protease involved in pancreatic homeostasis, immune-mediated diseases, and cancer risk.