Ferroptosis as a Nexus in Skeletal Muscle Pathophysiology: From Molecular Networks to Precision Medicine

Ferroptosis, an iron‐dependent cell death driven by lipid peroxidation, is a central pathological mechanism unifying diverse skeletal muscle disorders, including atrophy (e.g., sarcopenia, CKD), impaired regeneration, and acute injury. This review synthesizes recent evidence to map a multilayered regulatory network encompassing dysregulated iron/lipid metabolism, collapsed antioxidant defenses (e.g., GPX4, FSP1, GCH1), organelle cross‐talk, and complex signaling pathways (e.g., NRF2, p53). Critical translational gaps persist, such as a lack of human validation, insufficient understanding of context‐dependent regulation, and challenges in biomarker development. Future directions must prioritize human biomarker discovery, elucidate nonautonomous drivers (e.g., senescent macrophages), evaluate organelle‐targeted therapies, and advance biomarker‐stratified trials with repurposed drugs (e.g., SGLT2 inhibitors) to enable ferroptosis‐targeted precision medicine for muscle diseases.