Regenerating (Reg) gene family belongs to the calcium depending lectin gene super family. It represents a group of small, multi‑functional secreted proteins, which can function as acute phase reactants, lectins and anti‑apoptotic or growth agents. These agents play an important role in proliferation and differentiation in the entire GI tract. The Reg family consists of seven members in mice (Reg I, Reg II, Reg IIIa, Reg IIIb, Reg IIId and Reg IIIge and Reg IV). Four members are recognized in humans (Reg Ia, Reg Ib, Reg III and Reg IV), but there are most probably a few more. Reg genes are up‑regulated following tissue injury, and play a major role in the healing of gastrointestinal mucosal lesions. Different members of the Reg gene family were shown to be expressed in pancreatic, gastric and colorectal cancers, and may serve as markers for poor prognosis. Reg IV, a novel member of the family, was suggested to play an important role in initiating the multi‑step process of colorectal cancer carcinogenesis, at the level of adenoma, by increasing the resistance for programmed cell death. Regenerating gene family member 4 (REG4) was originally identified by sequencing of a cDNA library derived from patients with inflammatory bowel disease. It is located on chromosome 1, encoding 158 amino acids, including a signal peptide of 22 amino acids and a conserved calcium-dependent carbohydrate- recognition domain. Although REG4 is expressed in various normal tissues, the expression levels are much lower than in cancerous tissues. It is expressed not only in various normal tissues such as stomach, colon, small intestine and pancreas, but also in various malignant diseases, including colorectal, gastric, pancreatic and gallbladder cancer as well as in benign diseases such as ulcerative colitis.