Maureen Spit et al. showed that the environmentally independent self-renewal of cancer cells is driven by truncating mutations in RNF43, which prevent the degradation of β-catenin by immobilizing CK1 at the cell membrane, leading to the sustained activation of transcription of target genes, suggesting that truncating mutations in RNF43 play an important role in the development of cancer (Spit et al. 2020). The gene discussed is RNF43; the disease is cancer.