NRF2-activating mutations and loss of function mutations in KEAP1 and Cul3 that prevent effective NRF2 repression frequently occur in many cancers, such as liver cancer [97], lung cancer [98], ovarian cancer [99], kidney cancer [100], and breast cancer [101], resulting in constitutive activation of NRF2 signaling in cancer cells. The gene discussed is CUL3; the disease is cancer.