Roof plate-specific Spondin-1 (R-Spondin 1 or RSPO1), also known as CRISTIN3, is a 27 kDa secreted activator protein that belongs to the R-Spondin family. R-Spondins positively regulate Wnt/beta-catenin signaling, most likely by acting as a ligand for LGR4-6 receptors and an inhibitor for ZNRF3. R-Spondin-1 induces proliferation of intestinal crypt epithelial cells, increases intestinal epithelial healing, and supports intestinal epithelial stem cell renewal