We conclude that: (1) Nrf2 hyperactivation without concomitant autophagy impairment and aberrant p62 accumulation does not alter the observed liver injury and tumor burden in NEMOLPC-KO mice; (2) In contrast to its beneficial effect in mice with a hepatic autophagy defect, systemic p62 deficiency leads to perinatal lethality of NEMOLPC-KO mice; (3) Expression of a p62 mutant does not impair survival, but exacerbates hepatocarcinogenesis. The gene discussed is NFE2L2; the disease is neoplasm.