R-spondin-3 (RSPO3), also known as Protein with TSP type-1 repeat, Roof plate-specific spondin-3, Thrombospondin type-1 domain-containing protein 2, PWTSR, THSD2 and CRISTIN1, is a member of the thrombospondin type 1 repeat supergene family. RSPO3 is a secreted protein and widely expressed in many tissues. RSPO3 contains two Furin-like repeats which have been found in a variety of eukaryotic proteins involved in the mechanism of signal transduction by receptor tyrosine kinases, and one TSP type-1 domain, RSPO3 founctions as a activator of the beta-catenin signaling cascade, leading to TCF-dependent gene activation. Otherwise, RSPO3 may negatively regulate the TGF-beta pathway.