Reg4 is a member of a multigene family of Reg proteins. Reg proteins are secreted glycoproteins belonging to the calcium dependent lectin superfamily, although they can in fact bind polysaccharides, mannan, and heparin in the absence of calcium.Reg4 is expressed in the gastrointestinal tract, in normal colon mucosa, and is upregulated in colon adenocarcinoma, pancreatic cancer, gastric adenocarcinoma, and inflammatory bowel disease.It has recently been shown that Reg4 marks a population of deep secretory cells at the bottom of the crypts in the colon. In the upper gastrointestinal tract, Paneth cells support the Lgr5+ positive stem cells that reside at the base of deep crypts by providing signals such as Wnt3, EGF, and Notch ligands for stem cell maintenance. No Paneth cells, however, exist in the colon crypts. It is proposed that the Reg4+ population serves as an analogous support system for the LGR5+ positive stem cell population in the colon.
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