RSPO3 is a secreted protein that belongs to the R-spondin (RSPO) family. Interestingly, it is one of the two members (RSPO2 and RSPO3) of the family capable of potentiating WNT signaling in cells lacking all three LGRs (Leucine-rich repeat-containing G-protein-coupled receptor 4/5/6) []. RSPO3 promotes angioblast and vascular development []. It has been shown to promote bladder cancer progression via mediating the Wnt/beta-catenin and Hedgehog signaling pathways []. The R-spondin (RSPO) family is a small group of four secreted proteins (RSPO1-RSPO4) that have pleiotropic functions in development and stem cell growth by strongly enhancing Wnt pathway activation. They contain an N-terminal secretory signal peptide sequence, two tandem furin-like cysteine-rich (Fu-CRD) domains, a thrombospondin type I repeat (TSP) domain, and a C-terminal basic amino acid-rich (BR) domain. Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), LGR5, and LGR6 have been identified as receptors for RSPOs [].
