Conversely, in cultured breast cancer cells, VANGL proteins act as a scaffold for the ring finger-containing E3 ligase neuregulin receptor degradation protein 1 (Nrdp1; also called RNF41, FLRF or RBCC), which promotes the K63-linked polyubiquitination of the DEP domain of the Dvl proteins, thereby blocking Dvl binding to the plasma membrane (Wald et al., 2017). The gene discussed is TRIM17; the disease is breast cancer.