{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Four‐and‐a‐half LIM domains 1 (FHL1) is a multifunctional LIM‐only protein that acts as a versatile scaffold and signaling adaptor in striated muscle, where it integrates biomechanical cues with intracellular signaling pathways. In the heart, FHL1 localizes within the sarcomere by interacting with titin’s N2B region and modulates titin–MAPK mechanotransduction, which is critical for adapting to pressure overload and hypertrophic stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In skeletal muscle, FHL1 interacts with myosin‐binding protein C to influence thick filament assembly and is indispensable for proper myofibrillar organization and myogenic differentiation; disruptions in these interactions contribute to defective sarcomere assembly and impair muscle fiber formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mutations or dysregulated expression of FHL1 are linked to a spectrum of myopathies—including reducing body myopathy, scapuloperoneal myopathy, and X‐linked myopathy with postural muscle atrophy—as well as cardiomyopathies, where abnormal FHL1 function (via loss‐of‐function or poison peptide mechanisms) perturbs contractile function and cellular hypertrophic responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its structural roles, FHL1 also regulates gene expression by interacting with transcriptional modulators such as RIP140 to repress estrogen‐dependent transcription, and it is subject to epigenetic control in cancer cells, where its down‐regulation via promoter hypermethylation correlates with increased invasiveness in gastric, oral, and bladder carcinomas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, FHL1 participates in the regulation of cytoskeletal dynamics by partnering with proteins such as paxillin and the guanine nucleotide exchange factor PLEKHG2 to modulate cell adhesion, spreading, and migration, suggesting roles in both normal tissue remodeling and pathological conditions like pulmonary hypertension."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, FHL1 emerges as a critical node that couples structural integrity with signaling and transcriptional regulation in muscle cells. Its ability to integrate biomechanical, epigenetic, and cytoskeletal cues underlies its involvement in cardiac hypertrophy, muscle differentiation, and pathogenesis of both myopathic and oncogenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Farah Sheikh, Anna Raskin, Pao-Hsien Chu, et al. 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