The R-Spondin (Rspo) proteins belong to the Rspo family of Wnt modulators. Currently, the family consists of four structurally related secreted ligands (Rspo 1-4), all containing furin-like and thrombospondin structural domains. The Rspo proteins can interact with the Frizzled/LRP6 receptor complex in a manner that causes the stabilization and resulting accumulation of the intracellular signaling protein, β-catenin. This activity effectively activates and increases the subsequent nuclear signaling of β-catenin. R-Spondin can also bind to the previously discovered G-protein coupled receptors, LGR-4 and LGR-5. Rspo/β-catenin signaling can act as an inducer of the transformed phenotype, and can also regulate the proliferation an