{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCardiac myosin‐binding protein C (MYBPC3) is a critical sarcomeric protein whose normal function is essential for maintaining myocardial structure and ensuring proper contractile performance. Clinical genetic studies have shown that mutations in MYBPC3 represent the most common cause of hypertrophic cardiomyopathy (HCM) across diverse populations, and they are often associated with abnormal myocyte disarray and impaired relaxation. In both adult and pediatric cohorts—as well as in familial and sporadic cases—detection of MYBPC3 mutations has provided strong evidence for its central role in preserving cardiac morphology and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, the N‐ and C‐terminal regions of cardiac myosin‐binding protein C (cMyBP‑C) interact with both myosin and actin to modulate crossbridge kinetics and the recruitment of myosin heads from a “super‐relaxed” state. This phosphorylation‐dependent regulatory mechanism is crucial for fine‐tuning contractility, as kinase‐induced modifications accelerate crossbridge cycling and enhance force generation while also promoting efficient relaxation. In vitro and structural studies have detailed how mutations or truncations in MYBPC3 disrupt these interactions—by generating either dominant negative effects or haploinsufficiency—thereby altering sarcomere composition and energetics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther mechanistic insights have revealed that aberrant phosphorylation, truncation, or accelerated degradation of cMyBP‑C—often mediated by the ubiquitin–proteasome system—compromises its ability to restrain myosin head availability, thereby leading to hypercontractile states or impaired relaxation seen in both hypertrophic and dilated cardiomyopathies. In addition, studies on energetic cost of contraction and structural dynamics highlight how dosage-dependent depletion of cMyBP‑C disrupts the normal equilibrium of sarcomeric function, while emerging therapeutic approaches seek to correct these defects by modulating kinase activity and stabilizing sarcomere interactions. These findings underscore the importance of MYBPC3 not only as a structural scaffold but also as a dynamic regulator of contractile performance and as a promising target for intervention in cardiomyopathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sara L Van Driest, Vlad C Vasile, Steve R Ommen, et al. 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