The role of m6A RNA methylation in skeletal muscle pathophysiology and its targeted therapeutic prospects.

N6-methyladenosine (m6A) is the most abundant internal epitranscriptomic modification in eukaryotic mRNA. It dynamically regulates RNA splicing, transport, stability, and translation efficiency through the "Writers-Erasers-Readers" system, thereby playing a broad role in gene expression regulation. Skeletal muscle, a key metabolic and locomotor organ, undergoes precise m6A-mediated regulation during development, regeneration, homeostasis, and aging. In this review, we systematically summarize the composition and function of the m6A modification system, with a focus on its critical roles in skeletal muscle physiology, including satellite cell fate determination, myofiber differentiation and fusion, and energy homeostasis. Furthermore, we dissect the molecular mechanisms by which m6A network dysregulation contributes to skeletal muscle diseases such as sarcopenia, muscular dystrophy, muscle atrophy, metabolic myopathies, and fibrosis. The therapeutic potential of small-molecule drugs and intervention strategies targeting the m6A pathway is also discussed. This work provides a new epitranscriptomic perspective for the precise diagnosis and targeted therapy of skeletal muscle diseases.