Mucins are a family of large glycoproteins that create the structural component of mucus. Mucus functions as a blockade against pathogenic invasion and physical injury to the respiratory, gastrointestinal, and urogenital tracts. Mucins create a protective layer for epithelial cells as either membrane-bound (MUC1, MUC3, MUC16, and MUC17) or secreted (MUC2, MUC5AC, and MUC19) proteins. MUC2, or mucin-2, the main O-glycosylated protein found in mucus, is secreted by goblet cells. The structure of MUC2 contains cysteine-rich N- and C-terminal domains along with a protein core made up of heavily O-glycosylated mucin domains. The high levels of O-glycosylation along with disulfide bonding make MUC2 resistant to proteolytic cleavage. Mucin expression and glycan structure changes occur in cancers of the intestine and impact the development and progression of these cancers. The presence of MUC2 in the mucous layer of the colon helps prevent ulcerative colitis (UC) by inhibiting the invasion of bacteria.