The transcription factor NRF2 (Nuclear factor erythroid 2-related factor 2) orchestrates the cellular antioxidant defense controlling glutathione, thioredoxin, and iron/heme homeostasis, displaying a dual role in the brain: the preservation of neuronal–glial redox balance, yet, when persistently activated in glioblastoma, supporting glioma stem cell maintenance [6,8]. The gene discussed is NFE2L2; the disease is central nervous system cancer.