R-spondin-4 (RSPO4)

R-spondin-4 (RSPO4) is a secreted protein that belongs to the R-spondin family, characterized by a signal peptide, two cysteine-rich furin-like domains, a thrombospondin type-I repeat domain, and a basic amino acid-rich region[2][4][5]. RSPO4 functions as a potent agonist of the Wnt/β-catenin signaling pathway, acting primarily through its interaction with LGR4/5/6 receptors—key markers of stem and progenitor cells—thereby amplifying Wnt signals crucial for cell proliferation, cell adhesion, migration, and tissue development[2][3][4]. RSPO4 is essential for nail and limb development and its genetic disruption causes a congenital absence of nails (anonychia congenita)[1][5]. Mutations and deregulation of RSPO genes are associated with developmental disorders and implicated in cancer biology, largely due to their role in stem cell regulation and modulation of negative feedback regulators (ZNRF3/RNF43) in the Wnt pathway[3]. As a therapeutic target, RSPO4 is most relevant in contexts involving developmental biology, regenerative medicine, and oncology, but no approved drugs directly target RSPO4 as of now[3]. Safety concerns stem from the risk of excessive cell proliferation and tumorigenesis resulting from augmented Wnt signaling[3].

Other names

C20orf182CRISTIN4dJ824F16.3hRspo4roof plate-specific spondin-4R-spondin family member 4R-spondin-4RSPO4

Agonists or modulators enhance Wnt/β-catenin signaling by stabilizing or activating Wnt-pathway receptors through binding LGR4/5/6 and modulating ZNRF3/RNF43 turnover[2][3]