AGR2 is an endoplasmic reticulum (ER)-resident protein disulfide isomerase that plays critical roles in protein folding and mucus barrier function 1. The protein is essential for proper processing and secretion of gel-forming mucins, particularly MUC2, which forms the protective mucus layer in the gastrointestinal tract 23. AGR2 functions as a thioredoxin, catalyzing disulfide bond formation and assisting in protein quality control within the ER 4. Human AGR2 deficiency causes severe mucus barrier dysfunction, leading to infantile-onset inflammatory bowel disease characterized by goblet cell loss, reduced MUC2 expression, and increased ER stress 3. Beyond its physiological role, AGR2 acts as a proto-oncogene in various cancers, promoting cell migration, proliferation, and metastasis 56. In pancreatic cancer, secreted AGR2 activates cancer-associated fibroblasts through Wnt signaling, establishing a reciprocal signaling loop with IGF1 that promotes tumorigenesis 6. AGR2 expression is prevalent across multiple cancer types, particularly adenocarcinomas, and serves as both a diagnostic marker and prognostic indicator 7. The protein's dual role in maintaining intestinal homeostasis and promoting cancer progression makes it clinically significant for both rare genetic disorders and common malignancies.