The AMPK/SIRT1/PGC‐1α axis thus provides a multidimensional intervention strategy targeting core ALS pathologies including mutant protein clearance (SOD1 aggregates), oxidative damage control (ROS burst), and mitochondrial reprogramming (respiratory chain repair/neuromuscular junction maintenance), with these findings not only revealing a reversible window for motor neuron degeneration but also establishing the molecular foundation for a “neuro‐metabolic homeostasis remodeling” therapeutic paradigm in ALS treatment. Here, SOD1 is linked to amyotrophic lateral sclerosis.