R-Spondin-1, also known as Rspo-1, 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 LGR6 have been identified as receptors for all four R-Spondins. R-Spondin 1 is expressed in the nervous system during development and in endocrine tissues, especially in the gonads. It potentiates the signaling of Wnt-4 and antagonizes DKK-1 activity, and is crucial for the formation of female phenotype by opposing male phenotype development. R-Spondin 1 is also involved in the control of keratin formation, in the induction of cell proliferation in mucosal tissues, and in the inhibition of pro-inflammatory processes.