R-Spondin 2 (RSPO2) is a secreted protein belonging to the R-Spondin family of four structurally related Wnt/beta-catenin signaling regulators. All four members contain one thrombospondin-like and two furin-like domains. In adults, R-Spondin 2 is expressed in intestine and lung as well as other organs of endodermal origin. R-Spondins can enhance Wnt/beta-catenin signaling as they compete with the Wnt agonist DKK-1 for binding to Wnt co-receptors LRP6/Kremen. They can also act as a signaling activation ligand on LRP6 and LGR4 to form a cluster with WNT and FZD. The R-Spondins have been demonstrated to bind to LGR-4, LGR-5 and LGR-6 receptors with high affinity.