Skeletal muscle is a crucial motor organ composed of multinucleated myofibers, which form through cell differentiation, cell-cell fusion, myonuclei migration, and myofibril crosslinking. This review comprehensively discusses the physiological and pathological processes of skeletal muscles from five perspectives: molecular structure, myogenesis, biological functions, adaptive changes, and myopathy. The molecular structure section focuses on skeletal muscle-specific fusogens (myomaker and myomerger) and their roles in cell-cell fusion and myonuclei localization. The myogenesis section details the formation of myofibers, including the fusion process and myonuclei localization. The biological function section covers muscle contraction, thermogenesis, and myokine secretion, while the adaptive changes section discusses muscle atrophy, hypertrophy, and regeneration. The myopathy section explores diseases related to these processes. The review integrates these aspects to provide a holistic perspective on the structure, characteristics, and functions of skeletal muscles, offering insights into potential therapeutic targets for myopathies.Skeletal muscle is a crucial motor organ composed of multinucleated myofibers, which form through cell differentiation, cell-cell fusion, myonuclei migration, and myofibril crosslinking. This review comprehensively discusses the physiological and pathological processes of skeletal muscles from five perspectives: molecular structure, myogenesis, biological functions, adaptive changes, and myopathy. The molecular structure section focuses on skeletal muscle-specific fusogens (myomaker and myomerger) and their roles in cell-cell fusion and myonuclei localization. The myogenesis section details the formation of myofibers, including the fusion process and myonuclei localization. The biological function section covers muscle contraction, thermogenesis, and myokine secretion, while the adaptive changes section discusses muscle atrophy, hypertrophy, and regeneration. The myopathy section explores diseases related to these processes. The review integrates these aspects to provide a holistic perspective on the structure, characteristics, and functions of skeletal muscles, offering insights into potential therapeutic targets for myopathies.