ACTN2 encodes alpha-actinin-2, an F-actin cross-linking protein that functions as a structural anchor in the cardiac and skeletal muscle sarcomere Z-disk, where it links anti-parallel actin filaments and binds N-terminal titins to contribute to sarcomere stability 1. The protein organizes the actin cytoskeleton through its bundling and cross-linking activities 1. ACTN2 variants are implicated in diverse muscle pathologies with moderate evidence for disease association 2. Mutations cause autosomal dominant dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), with ACTN2 classified among genes with moderate evidence for DCM 2. Notably, ACTN2 is associated with autosomal dominant distal myopathy 3, and truncating variants show enrichment in left ventricular noncompaction (LVNC) cases 4. More recently, ACTN2 mutations have expanded the phenotypic spectrum to include congenital and distal myopathies beyond traditional cardiomyopathy presentations 1. Clinically, ACTN2 variants explain only a minority of DCM cases, and clear genotype-phenotype correlations remain limited despite growing evidence of its central role in muscle tissue pathogenesis 21. The functional mechanisms linking specific variants to distinct phenotypes (cardiomyopathy versus skeletal myopathy) require further investigation.