Core Viewpoint - Ferroptosis is a novel form of programmed cell death characterized by abnormal accumulation of iron ions and explosive generation of reactive oxygen species (ROS), leading to lipid peroxidation of cell membranes. Recent studies indicate its association with various diseases, including cancer and neurodegenerative disorders, making it a potential therapeutic target [2]. Group 1 - N-acetyl-L-cysteine (NAC) is widely recognized as an antioxidant in cell death research and is increasingly acknowledged for its role in inhibiting ferroptosis [2][5]. - The research team led by Professor Marcus Conrad published findings that NAC treatment can rapidly replenish intracellular cysteine pools, enhancing its function as a cysteine precursor [6]. - The study revealed that both NAC and its enantiomer D-NAC can act as direct reducing substrates for glutathione peroxidase 4 (GPX4), combating lipid peroxidation independently of glutathione synthesis [6][7]. Group 2 - The core findings of the study include that NAC and D-NAC can inhibit ferroptosis independently of cellular glutathione (GSH) [7]. - The presence of GPX4 is essential for NAC and D-NAC to exert their inhibitory effects on ferroptosis [7]. - GPX4 can utilize various reducing substrates to reduce lipid hydroperoxides, indicating a broader role for GPX4 in ferroptosis regulation [9].