RSPO4encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants.

The 224-amino acid human RSPO4 protein, like other members of the RSPO family, contains an N-terminal signal peptide, 2 furin-like domains, a thrombospondin type-1 (THBS1) domain, and a C-terminal low-complexity region enriched with positively charged amino acids. Dot blot analysis revealed very weak expression of RSPO4 in adult organs and tumors.