{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMYL4, an atrial‐specific myosin light chain, plays a critical role in maintaining normal atrial electrical and contractile properties. Recent genomic studies identified that loss‐of‐function mutations in MYL4, including a recessive frameshift mutation and a heterozygous p.Glu11Lys mutation, are implicated in early‐onset atrial fibrillation and atrial myopathy, with evidence from both human genetic associations and zebrafish models demonstrating sarcomeric disruption, atrial enlargement, and electrophysiological abnormalities. These findings support the idea that MYL4 gene defects can predispose to atrial arrhythmias by directly compromising the structural integrity and electrical conduction of the atrial myocardium."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, MYL4 encodes an essential light chain whose N-terminal region serves as a key actin binding domain. Biochemical and kinetic studies using recombinant proteins reveal that the first 11 to 45 amino acids of the N terminus mediate actin interaction and modulate actin-activated MgATPase activity. Mutational analyses have shown that precise alterations in this region, including substitutions or deletions, can significantly affect cross-linking to actin and modify the kinetics of the myosin motor, highlighting the crucial role of the N-terminal domain as both a binding interface and a regulator of contractile function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, altered expression of MYL4 has been linked to adaptive changes in cardiac contractility under pathological conditions. Evidence from studies in animal models suggests that re-expression of the atrial isoform of the myosin light chain in the ventricular myocardium can enhance contractile performance in hypertrophied hearts, and emerging biomarker studies propose that serum MYL4 levels, in combination with microRNA profiles, may have predictive value for the diagnosis and risk stratification of atrial fibrillation. These multifaceted roles underscore the importance of MYL4 both as a structural component of the sarcomere and as a potential clinical biomarker in cardiac disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Daniel F Gudbjartsson, Hannes Helgason, Sigurjon A Gudjonsson, et al. 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