The Wnt/β-cateninpathway is critical in humantumor progression.Cell-surface transmembrane E3 ubiquitin ligase ring finger 43 negativelyregulates Wnt signaling through ubiquitination of Wnt coreceptor Frizzled.Aberrant Wnt signaling through inactivating mutations of RNF43 hasbeen identified in various forms of cancers, highlighting its significancein tumor biology. The gene discussed is RNF43; the disease is cancer.