The transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) is a negative feedback regulator of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6 and acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway.