The role of Piezo1 in skeletal muscle physiology and pathology: from mechanosensing to precision therapy.

Skeletal muscle development, homeostasis, and repair rely on mechanical signals. Piezo1, a mechanosensitive cation channel, translates membrane lipid cues into intracellular responses. This review summarizes Piezo1's roles in skeletal muscle physiology and pathology. Physiologically, Piezo1 mediates calcium influx to regulate myogenesis, satellite cell quiescence/activation, myofibrillar protein synthesis/metabolism, and microvascular homeostasis. Pathologically, Piezo1 exhibits a dual nature: its downregulation drives disuse atrophy via the Piezo1/KLF15/IL-6 axis, while aberrant activation in Duchenne muscular dystrophy exacerbates myofiber damage and impairs regeneration. Piezo1 also amplifies post-injury inflammation and modulates intramuscular fat infiltration. We further discuss regulatory networks involving YAP/TAZ, TRP channels, the cytoskeleton, and membrane lipids, highlighting future challenges such as cell-type specificity, signal diversity, subcellular localization, and functional balance. Targeting Piezo1 holds therapeutic promise: agonists (e.g., Yoda1) counter atrophy and promote regeneration; inhibitors (e.g., GsMTx4) alleviate dystrophic damage; and low-intensity pulsed ultrasound enables non‑invasive spatiotemporal control. Thus, based on current evidence, Piezo1 is an important mechanotransducer in muscle biology and a novel target for precision therapies against atrophy, dystrophy, and sports injuries.