R-spondin 1 (RSPO1, Roof plate-specific Spondin 1) is a cysteine-rich secreted glycoprotein that belongs to the R-Spondin family. Structurally, R-spondin 1 harbors an N-terminal signal peptide, two cysteine-rich furin-like (FU1-FU2) domains, a thrombospondin (TSP) domain, and a basic amino acid-rich (BR) C-terminal domain. R-spondin 1 acts as a ligand for the leucine-rich repeat-containing G-protein coupled receptor (LGR) family (LGR4/5/6), subsequent clearing negative regulators ZNRF3/RNF43 from the membrane, leading to the availability of Wnt receptor and activating Wnt/beta-catenin signaling. The signal cascade is essential for regulating stem cell proliferation, embryonic development, and tissue homeostasis.
