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This process is driven by disrupted GSH homeostasis, resulting from diminished GSH synthesis and impaired activity of two critical antioxidant systems: (1) the cystine/glutamate antiporter xCT, which imports cystine to fuel GSH production and (2) GPX4, which utilizes GSH to convert lipid peroxides into less toxic lipid alcohols ( By degrading GSH, CHAC1 perturbs redox homeostasis and can effectively blunt the NRF2-driven cytoprotective response