This inhibition is generated by a non-canonical negative feedback loop of the Wnt/β-catenin signalling a pathway mediated by the interaction of RSPO2 with the G-protein-coupled receptor 5 containing leucine-rich repeats (LGR5), which stabilizes the, membrane-associated zinc and ring finger 3 (ZNRF3) and results in impaired cell proliferation, at least in the context of p53−/− or LGR5-competent CRC cell lines. The gene discussed is XCR1; the disease is colorectal carcinoma.