TPM1 (tropomyosin 1) is a cytoskeletal protein that binds to actin filaments in both muscle and non-muscle cells 1. In striated muscle, TPM1 plays a central regulatory role in calcium-dependent contraction through association with the troponin complex 1. The protein stabilizes actin filaments and regulates muscle filament sliding during sarcomere organization. Beyond its contractile functions, TPM1 is involved in cytoskeletal organization and cellular responses to stress, including reactive oxygen species signaling and wound healing. TPM1 mutations are associated with three primary cardiomyopathic conditions: familial hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and left ventricular non-compaction (LVNC). In HCM, TPM1 is classified as having definitive evidence for disease causation 2. For DCM, TPM1 variants are significantly enriched in patient subsets and represent moderate-level evidence, potentially contributing to early-onset forms 34. Recent studies demonstrate that site-specific lysine crotonylation of TPM1 at K28/29 is critical during myocardial ischemia-reperfusion injury, where modulation of this post-translational modification protects cardiomyocytes from apoptosis and preserves myocardial function 5. Clinically, TPM1 mutations show variable penetrance and disease severity across cardiomyopathy subtypes, making it an important gene for diagnostic genetic testing in familial cardiomyopathy screening.