GJA1 and neoplasm: Loss of Cx43 causes neonatal lethality owing to the defects in the heart and nervous systems during development.94, 95, 96 Also, mutation and loss of Cx43 expression promote tumorigenesis and metastasis in the DMBA‐induced tumor model.97 NEDD4 is the first ubiquitin ligase that has been reported to mediate internalization and degradation of Cx4398 (Figure 6A).