R-Spondin 3, also known as Rspo-3, is a growth factor belonging to the R-Spondin family. R-Spondins are four proteins that support adult stem cell proliferation, and act as Wnt modulators by signaling through the canonical Wnt/β-catenin pathway as agonists. LGR4, LGR5, and LGR& have been identified as receptors for all four R-Spondins. R-Spondin 3 enhance Wnt-1, Wnt-3a, and Wnt-7a activity and antagonizes DKK-1. It is expressed by several tissues during placental and embryonic development, where it plays an important role in vascular formation. An involvement of R-Spondin 3 was also found in tumor tissues and in the growth of the gastrointestinal epithelium. Human R-Spondin 3 shares 88% protein sequence homology with mouse R-Spondin 3.