ACTC1 encodes α-cardiac actin, a sarcomeric thin-filament protein essential for cardiac muscle contraction and myofibril assembly 1. As a highly conserved actin isoform, ACTC1 participates in actin-myosin filament sliding and actomyosin structure organization critical for cardiac function 2. Loss-of-function mutations in ACTC1 are definitively associated with hypertrophic cardiomyopathy (HCM), with 8 sarcomeric genes including ACTC1 classified as having definitive evidence for HCM causation 3. ACTC1 also shows moderate evidence for dilated cardiomyopathy (DCM) susceptibility and is among 12 genes robustly associated with monogenic DCM that explain approximately 17-26% of cases 42. Thin-filament mutations including ACTC1 variants present a distinct HCM phenotype characterized by milder left ventricular hypertrophy but progressive dysfunction and increased heart failure risk compared to thick-filament disease 1. The pathogenic mechanisms involve disrupted sarcomeric architecture and altered cellular mechanics, with emerging evidence that immune dysfunction contributes to adverse remodeling in ACTC1-associated HCM 5. Penetrance of HCM in ACTC1 mutation carriers is incomplete, with male sex and abnormal electrocardiograms predicting higher disease progression risk 6.