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/β-catenin signaling. The signal cascade is essential for regulating stem cell proliferation, embryonic development, and tissue homeostasis.