Interestingly, the non-canonical activators of NRF2 are primarily involved in the regulation of disparate cellular functions such as autophagy (p62), protein turnover (DPP3), DNA repair (PALB2), cell cycle, and apoptosis (p21, Prothymosin α), while WTX and BRCA1 are well-known oncosuppressors that control genomic stability, cell-cycle progression, cell migration, and stem-cell pluripotency, thus emphasizing the complexity of NRF2 signaling and its intimate connection with cancer. The gene discussed is NFE2L2; the disease is cancer.