Mucin 2 (MUC2) is an oligomeric mucus gel-forming protein coded by the MUC2 gene at chromosome 11p15.5. The protein is secreted by intestinal goblet cells to the gut where it constitutes the main component of colorectal mucus. The mucins function as a defense mechanism to maintain the integrity of the epithelial cells which are continuously exposed to luminal contents that include large quantities of different bacteria, proteases, bile, and ingested toxins. The mucin barrier consists of two layers. The inner layer is directly attached to the epithelium, densely packed, largely consists of uncleaved MUC2, and is free from bacterial colonization. The outer layer contains bacteria and is less dense due of proteolytic cleavage of MUC2. Under normal conditions, the protease-resistant mucus layer prevents intestinal bacteria to make physical contact with epithelial cells by virtue of its only minute pore sizes and strong hydrophobic properties capable to repel bacteria in the aqueous lumen. Loss of MUC2 confers a microenvironment in which bacteria can activate an inflammatory response at the epithelial surface. The defensive function of MUC2 and of other mucins to maintain the integrity of the epithelial cells can also be exploited by tumor cells in limiting the activation of inflammatory responses.