myotilin

Myotilin is a human protein encoded by the MYOT gene and a member of the Z-disc–associated proteins of the sarcomere. It localizes to the Z-discs of striated muscle fibers in both skeletal and cardiac muscle. The protein features two C-terminal immunoglobulin-like domains that mediate interactions with actin filaments and other Z-disc components.

Functionally, myotilin contributes to the structural integrity of the sarcomere by binding filamentous actin and associating with Z-disc proteins, helping to organize and stabilize the Z-disc during muscle contraction. It is expressed in developing and mature muscle tissue and is concentrated at the Z-disc in mature fibers.

Pathogenic variants in MYOT cause myotilinopathies, most notably limb-girdle muscular dystrophy type 1A and distal myopathy. These conditions are typically inherited in an autosomal dominant manner and present with proximal muscle weakness, sometimes scapular winging, and elevated serum creatine kinase. Muscle biopsy often shows myofibrillar disorganization with protein aggregates, and immunohistochemistry can reveal abnormal accumulation of myotilin. Genetic testing identifying MYOT mutations confirms the diagnosis.

Diagnosis and management rely on genetic testing and supportive care. Myotilinopathy is considered part of a group of conditions affecting the Z-disc and myofibrillar organization, collectively referred to as myofibrillar myopathy or myotilinopathy. Ongoing research investigates the precise molecular mechanisms of MYOT-related disease and the vulnerability of Z-disc architecture in skeletal and cardiac muscle.