In agreement with our metabolomic and lipidomic datasets showing depletion of GSH metabolites and TAGs following rescue by CBP/p300-deficient NRF2, CBP/p300 was required for robust expression of GCLC. The finding that proliferation of NRF2-dependent cancer cells was unaffected by these considerable transcriptional, metabolomic, and lipidomic disruptions in response to CBP/p300 loss-of-function implies that the classical function of NRF2 in enhancing antioxidant capacity does not fully explain its role in cancer cell maintenance. Here, GCLC is linked to cancer.