{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlpha‐sarcoglycan, the protein encoded by the SGCA gene, is a critical component of the dystrophin‐associated glycoprotein complex that links the intracellular cytoskeleton to the extracellular matrix in muscle fibers. Its proper expression is essential for maintaining sarcolemmal integrity and mechanical stability during muscle contraction. Loss or mutation of SGCA disrupts this complex, and studies have demonstrated that restoring SGCA expression—whether by adeno‐associated viral gene transfer or by correcting splicing defects with precise gene editing—can improve muscle quality and function in patients with limb‐girdle muscular dystrophy type 2D (LGMD2D) and related sarcoglycanopathies."}, {"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": "\nBeyond its structural role, alpha‐sarcoglycan participates in key protein–protein interactions that regulate assembly and stabilization of the entire sarcoglycan complex at the membrane. For example, its interaction with extracellular matrix components such as biglycan helps modulate its localization and abundance. In addition, the regulation of SGCA gene transcription through promoter elements responsive to myogenic factors like MyoD underlines its dynamic expression during muscle differentiation. Furthermore, cellular quality control mechanisms that target misfolded SGCA—mediated by specific E3 ligases—highlight the importance of maintaining proper protein folding, with emerging pharmacological strategies showing promise in rescuing mutant SGCA expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn diagnostic and genetic studies, reduced or aberrant alpha‐sarcoglycan expression has proven invaluable for the evaluation of muscular dystrophies. Immunohistochemical analyses of muscle biopsies routinely incorporate assessment of SGCA to differentiate LGMD2D from other dystrophies, while genetic screening reinforces its role by linking specific mutations to distinct phenotypic outcomes—including variable onsets and severities of muscle degeneration and respiratory involvement. Moreover, genome‐wide association studies have identified loci proximal to SGCA that may contribute to conditions beyond classic muscular dystrophy, underscoring its broader biological relevance. Together, these investigations have provided a comprehensive view of SGCA’s function in maintaining muscle integrity and have paved the way for targeted therapeutic interventions in neuromuscular disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M C Walter, G Dekomien, B Schlotter-Weigel, et al. 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