MUC2 is a major secretory mucin that forms protective hydrogels coating intestinal epithelia 1. Synthesized by goblet cells, MUC2 polymerizes into large gel-forming networks through disulfide bonds, accounting for ~80% oligosaccharide content of mucus by weight 2. Its primary function is providing a physical barrier preventing direct bacterial contact with epithelial cells while permitting nutrient absorption and gas exchange 31. Beyond protection, MUC2 functions as a divalent copper chaperone, binding both Cu(2+) and Cu(1+) at juxtaposed sites to facilitate nutritional copper uptake while protecting cells from copper toxicity 4. The mucus layer stores antimicrobial molecules for innate immunity and feeds the microbiota 1. MUC2 expression patterns carry clinical significance: decreased expression occurs in colonic cancer, with MUC2 expression associated with indolent tumor behavior and favorable prognosis, contrasting with aggressive MUC1/MUC4-expressing neoplasms 25. In colorectal cancer, MUC2 functions as a physical barrier limiting immune infiltration 6. MUC2 dysfunction contributes to ulcerative colitis pathogenesis, making the mucus barrier and related bacterial factors therapeutic targets 3. Gene regulation involves epigenetic mechanisms including DNA methylation and histone modification 5.