{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Leiomodin‐3 (LMOD3) is a muscle‐specific actin nucleator that plays a central role in establishing and maintaining proper sarcomere structure in skeletal and cardiac muscle. It localizes along the actin thin filaments—particularly enriched near the pointed ends—where it robustly nucleates actin assembly to ensure correct filament elongation and spatial organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " LMOD3 function is further modulated by its binding partner KLHL40, which protects it from ubiquitination and degradation so as to sustain adequate levels of thin filament components; such stabilization is critical for normal muscle contractility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In vivo loss‐of‐function studies indicate that LMOD3 is indispensable for sarcomere integrity; its deficiency leads to disorganized and shortened thin filaments, formation of nemaline bodies, and even fast fiber–specific atrophy—all hallmarks of nemaline myopathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " In cultured myoblasts, LMOD3 not only promotes actin filament formation but also facilitates both differentiation and proliferation through activation of the AKT and ERK signaling pathways, emphasizing its role in muscle development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Complementary embryological studies reveal that appropriate levels of LMOD3—as well as its functional interplay with related capping proteins—are required during de novo myofibrillogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Intriguingly, emerging evidence associates rare LMOD3 variants with periodic hypersomnolence and neurodevelopmental features, suggesting that its role may extend beyond traditional muscle biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings establish LMOD3 as an essential regulator of actin dynamics and sarcomere assembly whose disruption underlies the pathogenesis of nemaline myopathy and may contribute to other neuromuscular and neurodevelopmental disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michaela Yuen, Sarah A Sandaradura, James J Dowling, et al. 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