{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n COL6A1 encodes the major α1 chain of collagen VI, an essential extracellular matrix protein that assembles into a microfibrillar network to maintain tissue structural integrity and regulate cell–matrix interactions. In skeletal muscle, collagen VI is critical for proper myofiber function, as it contributes to the regulation of autophagy, mitochondrial homeostasis, and apoptosis; defects in COL6A1 in murine models result in impaired autophagic flux, mitochondrial dysfunction, and increased myofiber cell death, thereby promoting muscular dystrophy phenotypes (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Furthermore, collagen VI plays a pivotal role in sustaining the satellite cell niche, as its presence ensures proper biomechanical properties and supports satellite cell self‐renewal during muscle regeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Mutations in COL6A1, acting via dominant-negative mechanisms or through disrupted protein assembly, cause a spectrum of collagen VI–related myopathies—including Bethlem myopathy and Ullrich congenital muscular dystrophy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond muscle, genetic studies have identified polymorphisms in COL6A1 that are strongly associated with ectopic ossification disorders such as ossification of the posterior longitudinal ligament and diffuse idiopathic skeletal hyperostosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In the nervous system, collagen VI exhibits neuroprotective properties by binding amyloid‐β oligomers, thereby reducing their toxic effects on neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, regulation of COL6A1 expression has been observed in the context of tumor and stromal interactions, suggesting that its modulation may influence extracellular matrix remodeling in certain cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings demonstrate that COL6A1 is multifunctional—playing a central role in extracellular matrix integrity, mechanotransduction, cell survival, and tissue repair, while its dysregulation contributes to a range of pathological conditions from muscular dystrophies to aberrant bone formation and neurodegenerative processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paolo Grumati, Luisa Coletto, Patrizia Sabatelli, et al. 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