Second, it reconciles seemingly disparate findings through a redox-metabolic lens—e.g., dual roles of HO-1 (protective via heme degradation vs. pro-ferroptotic via iron release) or iron overload (driving injury in AKI vs. targeted therapy in RCC)—by clarifying disease-specific regulatory mechanisms: PKD1 mutation-driven mitochondrial defects in ADPKD, DPP9-Nrf2-mediated sorafenib resistance in RCC, and PPARα–FABP1 axis dysregulation in IgA nephropathy, alongside shared core pathways (e.g., GPX4/SLC7A11 as central checkpoints). This evidence concerns the gene NFE2L2 and autosomal dominant polycystic kidney disease.