REG3A (regenerating family member 3 alpha) is a calcium-dependent lectin protein primarily expressed in gastrointestinal epithelial cells and pancreatic acinar cells 1. It functions as a multifaceted antimicrobial and immunomodulatory protein that reinforces epithelial barrier integrity, regulates host-microbiota interactions, and acts as a non-enzymatic antioxidant protecting tissues from oxidative stress 2. REG3A is secreted and binds to carbohydrates including glucose and glucose-6-phosphate 3. Its expression is induced by inflammatory stimuli and bitter taste receptor activation in the intestine, triggering antimicrobial peptide release and innate immune responses 4. REG3A's role in disease is context-dependent. In hepatocellular carcinoma, it acts as a tumor suppressor by reducing O-GlcNAcylation and c-MYC modification, with high hepatic REG3A expression correlating with longer cancer-free survival in cirrhotic patients 3. Conversely, in pancreatic ductal adenocarcinoma and triple-negative breast cancer, REG3A promotes tumor progression through EGFR-MAPK signaling activation and Akt-mTOR pathway stimulation, respectively 56. In sepsis-associated acute kidney injury, elevated urinary REG3A associates with an inflammatory immune phenotype and bacteremia risk 7. These opposing oncogenic effects likely reflect tissue-specific differences and microenvironmental context, establishing REG3A as a pleiotropic regulator with potential therapeutic significance across inflammatory and malignant diseases.