R-Spondin-3 is a member of thrombospondin type 1 repeat (TSR-1) superfamily that is involved in the canonical Wnt/β-catenin signaling pathway (de Lau et al.). R-spondin proteins are characterized by two furin-like repeats at the amino terminus and thrombospondin domain located near the carboxyl terminus (de Lau et al.). R-spondin-3 expression is associated with ovarian cancer (Gu et al.), prostate cancer (Mesci et al.), and differentiation of intestinal epithelial cells in diabetes mellitus (Shan et al.). In a transgenic mice model, the expression of R-Spondin-3 induces the expansion of Lgr5+ stem cells, Paneth cells, and Lgr4+ cells, promoting the intestinal stem cell compartment (Hilkens et al.). This protein contains a His-residue tag at the carboxyl end of the polypeptide chain.