MAFG (MAF bZIP transcription factor G) is a small basic-zipper transcription factor that functions primarily as a transcriptional repressor when forming homodimers, but acts as a transcriptional activator when heterodimerizing with larger bZIP proteins like NFE2L2 1. MAFG regulates antioxidant and anti-inflammatory gene expression by interacting with NRF2/NFE2L2 at specific DNA-binding sites and recruiting coactivators such as MYH9 23. Mechanistically, MAFG controls ferroptosis—iron-dependent programmed cell death—by transcriptionally activating ferroptosis-suppressor genes including lipocalin 2 (LCN2), heme oxygenase-1, and quinone oxidoreductase-1 234. MAFG also cooperates with MAT2α to promote DNA methylation and repress antioxidant programs 5. Clinically, MAFG dysregulation is implicated in multiple pathological conditions. Elevated MAFG expression in astrocytes drives CNS inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis 5. In hepatocellular carcinoma and liver fibrosis, MAFG suppresses ferroptosis in stellate cells, promoting fibrosis progression; therapeutic targeting via ferroptosis induction shows promise 3. MAFG also mediates immune suppression and stemness reprogramming in HCC 6, and its stabilization contributes to placental inflammation in placenta accreta spectrum 7. NRF2-MAFG complex disruption enhances chemotherapy sensitivity in KEAP1-deficient lung cancers 8.