RNF213 and neoplasm: Banh et al. found that protein-tyrosine phosphatase-1B (PTP1B) controlled non-mitochondrial oxygen consumption by regulating RNF213 to promote tumor survival during hypoxia and concluded that PTP1B/RNF213/α-KGDD pathway was critical for survival of tumors in the hypoxic microenvironment [51] The investigation of WNT signaling and PTP1B/RNF213/α-KGDD pathway in cells expressing RNF213 R4810K and other rare variants under different environmental condition such as hypoxia and chronic inflammation is expected to provide answers to the pending questions.