R-spondin-1 (RSPO1)

R-spondin-1 (RSPO1) is a secreted, cysteine-rich protein and a critical agonist of the canonical Wnt/β-catenin signaling pathway, functioning through binding to the receptors LGR4, LGR5, or LGR6 on the cell surface[1][2][3][4]. It plays essential roles in embryonic tissue development, stem cell maintenance, and female sex determination by synergistically activating Wnt signaling and promoting cell proliferation. RSPO1 is necessary for proper ovarian and gonadal differentiation—mutations can cause 46,XX sex reversal and predispose to certain skin cancers[1][3]. In adult tissues, RSPO1 is required for epithelial regeneration (notably in the intestine and oral mucosa) and bone homeostasis, with emerging relevance in therapeutic tissue repair, but excessive signaling has been implicated in tumorigenesis and fibrosis[2][3]. Recent research also shows RSPO1 promotes estrogen receptor alpha expression in mammary tissue via a Wnt-independent, cAMP-dependent pathway, broadening its functional repertoire and impact in hormone-responsive tissues[4].

Other names

R-spondin-1RSPO1hRspo1FLJ40906RSPONDINRoof plate-specific spondin-1CRISTIN3R-spondin homologroof plate-specific spondin-1

Agonist of LGR4/5/6 receptors, enhancing canonical Wnt signaling; Activator of cAMP-PKA-CREB pathway through GPCR mechanism (Wnt-independent ERα regulation)[4]; Inhibitor of ZNRF3/RNF43 E3 ubiquitin ligases, leading to stabilization of Wnt receptor complexes[2][3]