Although the pancreatic regenerating (reg) gene, was first isolated from a rat regenerating islets in 1988, its protein product was originally described in the 1970s. Reg proteins arise from a multigene family with three subtypes, and have a protein structure similar to calcium dependent lectins. Reg I and II have been implicated in control of pancreatic development and may play a role in maintenance of the beta-cell mass in the mature pancreas. Administration of reg I protein has been used in experimental animals as a therapy for surgically-induced diabetes mellitus. Reg I protein is also an inhibitor of calcium carbonate crystalization, important in maintaining the fluidity of pancreatic juice. The reg III gene, whose protein product is pancreatitis associated protein, is induced during pancreatic inflammation. Serum levels of reg III protein are a sensitive marker of severity of pancreatitis. It is an endogenous pancreatic factor that prevents the bacteria infection and scavenges oxygen-derived free radicals. Reg mRNA has been detected in non-pancreatic tissue such as the enterochromaffin-like cells of the stomach, neoplastic tissues of the colon, the small intestine, nervous system, liver tumors, and pituitary. Reg proteins are mitogens to intestinal epithelial cells, pancreatic ductal, beta cells, and Schwann cells, and are likely important to the overall integrity of the pancreas and gastrointestinal tract.