ZNRF3 and neoplasm: These two enzymes also function as tumor suppressors, as evidenced by the promotion of intestinal and adrenal hyperplasia (Koo et al. 2012; Basham et al. 2019) and hepatocellular carcinogenesis (Mastrogiovanni et al. 2020) upon tissue-specific inactivation of Znrf3/Rnf43. Similarly, Rnf43 deficiency leads to thickened mucosa, hyperplasia, and cellular atypia in the stomach (Neumeyer et al. 2019), and enhanced tumor growth in a mouse model of inflammatory colorectal cancer (Eto et al. 2018).