The Sarcomeric Spring Protein Titin: Biophysical Properties, Molecular Mechanisms, and Genetic Mutations Associated with Heart Failure and Cardiomyopathy

Purpose of Review The giant protein titin forms the “elastic” filament of the sarcomere, essential for the mechanical compliance of the heart muscle. Titin serves a biological spring, and therefore structural modifications of titin affect function of the myocardium and are associated with heart failure and cardiomyopathy. Recent Findings In this review, we discuss the current understanding of titin’s biophysical properties and how modifications contribute to cardiac function and heart failure. In addition, we review the most recent data on the clinical impact and phenotype heterogeneity of TTN truncating variants, including diseases involving striated muscles, and prospects for future therapies. Summary Because of the giant structure of the titin protein and the complexity of its function, titin’s role in health and disease is not yet completely understood. Future research efforts need to focus on novel therapeutic approaches able to modulate titin transcriptional and post-translational modification.