Mucin is a high-molecular-weight glycoprotein that is synthesized, stored, and secreted by epithelial mucosal cells, especially goblet cells. Mucin proteins are derived from many different genes, termed MUC genes. Several lines of evidence point to a biological role for mucin in cholesterol gallstone formation. Mucin serves as a pronucleating agent in experimental and human gallstone disease, and the hydrophobic binding sites in the polypeptide core of mucin may provide a favorable environment for nucleation of cholesterol monohydrate from supersaturated bile. Mucin hypersecretion is prominent in many animal models of gallstone formation, thus contributing by its pronucleating quality to gallstone formation. According to some research, mucin hypersecretion may also contribute to the formation of brown pigment stones. This may be explained in part by the findings that lipopolysaccharides derived from certain bacteria are effective stimulants of mucin secretion. Aspirin and nonsteroidal anti-inflammatory drugs inhibit gallbladder mucin secretion and prevent gallstone formation in animal models. Expanding our knowledge on mucin research may improve our understanding of the natural history of gallstone formation and enable the development of new treatment strategies.