Bile supersaturation is necessary for cholesterol gallstones to form. Not all people with supersaturated bile form gallstones, however, and additional factors must be present. The role of pronucleating substances has been extensively studied. Of these, proteins, especially mucin, are best understood. Mucin is secreted by the gallbladder epithelium and may act as a nidus for crystal nucleation. Other proteins that may act as pronucleators include alpha 1-acid glycoprotein, alpha 1-antichymotrypsin, phospholipase C, and a small calcium binding protein. The role of antinucleating factors is less well understood. Certain drugs, including octreotide and ceftriaxone, may also predispose to stone formation. Another local factor is gallbladder stasis, a well-known risk factor for pigment stone formation. More recent research has focused on the role of bacterial infection, which has long been believed to be a factor in pigment gallstone formation. Newer data also support a role for infection in cholesterol gallstone pathogenesis. Additionally, genetic factors that may predispose a patient to cholesterol gallstones have been identified in mice and in humans.