The Role of TXNIP in Skeletal Muscle Physiology and Related Diseases: Current Perspectives.

Abstract

Thioredoxin-interacting protein (TXNIP) is a multifunctional regulatory protein of the α-arrestin family that acts as a redox sensor, an energy-responsive molecule, and a transcription-associated regulator. TXNIP has emerged as a key regulator of skeletal muscle homeostasis and has been implicated in the pathogenesis of multiple muscle disorders. Skeletal muscle is a principal site of systemic glucose disposal, accounting for more than 70% of insulin-stimulated glucose uptake in the human body. TXNIP has been implicated in sarcopenia, obesity-related insulin resistance, limb ischemia-induced muscle injury, disuse muscle atrophy, and hereditary muscular dystrophy through multiple mechanisms, including glutathione metabolic regulation, ferroptosis, NLRP3 inflammasome activation, impaired GLUT4 membrane translocation, and altered mitochondrial substrate oxidation. Recent advances in gene editing, single-cell sequencing, metabolomics, and human clinical research have enabled a more detailed characterization of TXNIP-related molecular mechanisms in skeletal muscle. This review provides a systematic synthesis of recent evidence on TXNIP in skeletal muscle, organized around seven themes: its molecular characteristics, expression and regulatory patterns in skeletal muscle, physiological functions, disease-specific pathogenic mechanisms, intervention-related regulatory networks, current limitations, and future perspectives. This review aims to provide a mechanistic rationale for targeting TXNIP as a potential strategy for the prevention and treatment of skeletal muscle-related diseases.