MYBPC3 encodes cardiac myosin binding protein C (cMyBP-C), a thick filament-associated structural protein essential for regulating cardiac muscle contraction. It localizes to the A band and C zone of the sarcomere, where it binds myosin heavy chain, F-actin, and thin filaments to modulate actin-activated myosin ATPase activity and control muscle filament sliding 1. MYBPC3 functions as a dosage-dependent regulator of myosin contractility; stepwise depletion reciprocally augments myosin contractility and alters dynamic myosin conformations during relaxation, reducing the energy-conserving super relaxed state 1. MYBPC3 mutations are the most common genetic cause of hypertrophic cardiomyopathy (HCM), accounting for approximately 30-60% of familial cases 2. Approximately 91% of pathogenic variants are truncating mutations causing loss-of-function through haploinsufficiency, while remaining nontruncating variants cluster in C3, C6, and C10 domains 3. Truncating variants generate unstable mutant transcripts with mutant:wild-type ratios of approximately 1:5, yet total MYBPC3 mRNA increases 9-fold in mutant hearts, suggesting compensatory upregulation 4. Clinical manifestations range from asymptomatic to sudden cardiac death and advanced heart failure, with variable penetrance influenced by mutation type and genetic background 5. Recently, AAV9-mediated gene therapy with optimized expression cassettes reversed cardiac hypertrophy and systolic dysfunction in MYBPC3-deficient models 6, offering promising therapeutic potential for this prevalent cardiomyopathy.