English: Figure 3  The major activating inputs and functional outputs of the NRF2 pathway. NRF2 is activated in response to oxidative stress, metabolic stress, and various oncogenic stress signals upstream. NRF2 is a pleiotropic transcription factor that induces the expression of a plethora of downstream target genes. Highlighted are some of the most well-studied functional outputs of the NRF2 pathway. Glutathione (GSR, GCLC, GCLM, GPX2, and SLC7A11), multidrug resistance–associated proteins (ABCC1 and ABCC2), and thioredoxin (TXN1, PRDX1, TXNRD1, and SRXN1) metabolism proteins mediate detoxification of ROS, drugs, and toxins (see Table 1). The glucose-dependent pentose phosphate pathway enzymes G6PD and PGD and the central carbon metabolism enzymes ME1 and IDH1 increase the reducing capacity of cells by regenerating NADPH. Heme degradation by HMOX1 and iron sequestration by FTL1 and FTH1 maintain heme and iron homeostasis, preventing iron accumulation and ferroptosis.