MYL4 (myosin light chain 4) is a regulatory light chain component of myosin II complexes that plays critical roles in cardiac muscle contraction and conduction system function 1. The protein serves as a specific biomarker for cardiac Purkinje fibers, with MYL4-positive fibers comprising over 60% of human myocardial conduction system content, including a previously unrecognized deep intramural network 1. In cardiac pathophysiology, MYL4 expression is significantly altered in various disease states. Decreased MYL4 levels are associated with atrial fibrillation risk and severity, with lower serum levels correlating with higher thromboembolism risk scores and worse prognosis 2. MYL4 mutations cause familial atrial fibrillation through disrupted cellular mechanisms including abnormal connexin-43 localization, altered retinoic acid signaling, and metabolic dysfunction involving NAD+ depletion 3. The protein also shows increased expression in cardiac hypertrophy models and LMNA-associated dilated cardiomyopathy 45. Additionally, MYL4 expression increases in muscle regeneration areas of Duchenne muscular dystrophy and serves as a biomarker in end-stage renal disease 67. These findings establish MYL4 as both a structural component of cardiac conduction and a disease biomarker across multiple pathological conditions.