Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with<br>accessory proteins. Thick filaments occupy the center of sarcomeres where they partially overlap<br>with thin filaments. The sliding of thick filaments past thin filaments is a highly regulated process<br>that occurs in an ATP-dependent manner driving muscle contraction. In addition to myosin that<br>makes up the backbone of the thick filament, four other proteins which are intimately bound to the<br>thick filament, myosin binding protein-C, titin, myomesin, and obscurin play important structural<br>and regulatory roles. Consistent with this, mutations in the respective genes have been associated<br>with idiopathic and congenital forms of skeletal and cardiac myopathies. In this review, we aim to<br>summarize our current knowledge on the molecular structure, subcellular localization, interacting<br>partners, function, modulation via posttranslational modifications, and disease involvement of<br>these five major proteins that comprise the thick filament of striated muscle cells.