R-spondin3 （RSPO3）, an activator of Wnt/β-catenin signaling, plays a key role in tumorigenesis of various cancers. RSPO3 contains two adjacent cysteine-rich furin-like domains （aa 35-135） with one potential N-glycosylation site （aa 36）, followed by a thrombospondin （TSP-1） motif （aa 147-207） and a region rich in basic residues （aa 211-269）. RSPO3 is a novel contraction-inducible myokine produced by cultured human myotubes. Human RSPO3 is a paracrine factor that may positively participate in the myogenesis processes of myoblasts and satellite cells. RSPO3 promotes the tumor growth of choriocarcinoma via Akt/PI3K/ERK signaling, which supports RSPO3 as an oncogenic driver promoting the progression of choriocarcinoma. RSPO3 plays a role in the regulation of Wnt （wingless-type MMTV integration site family）/beta-catenin and Wnt/planar cell polarity （PCP） signaling pathways, which are involved in development, cell growth and disease pathogenesis. Genome-wide association studies suggest a correlation of this protein with bone mineral density and risk of fracture.?