{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n COL19A1 encodes type XIX collagen, a minor nonfibrillar member of the FACIT family that plays multifaceted roles in tissue development and homeostasis. Its developmental expression is dynamic, with early transcription in myogenic tissues that is subsequently maintained or upregulated in specific brain regions such as the hippocampus and telencephalic interneurons, suggesting key roles in both muscle differentiation and neural maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the central nervous system, type XIX collagen is critical for proper inhibitory synaptogenesis and the assembly of perineuronal nets, with its loss leading to altered synaptic architecture and behavioral abnormalities, indicating that extracellular matrix integrity is essential for normal neuronal connectivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In parallel, within skeletal muscle and esophageal tissues, COL19A1 is indispensable for normal muscle physiology—its deficiency results in disorganized extracellular matrix structure, impaired smooth muscle relaxation, and failed smooth-to-skeletal muscle cell conversion, ultimately compromising sphincter function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Beyond structural roles, the proteolytic NC1 domain of type XIX collagen generates matricryptins that exhibit anti-tumor and anti-angiogenic activities by modulating matrix metalloproteinases and integrin-mediated signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, elevated COL19A1 expression in muscle has emerged as a prognostic biomarker in amyotrophic lateral sclerosis, where higher protein levels correlate with faster disease progression and increased mortality."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, expression in cardiac fibroblasts and smooth muscle cells hints at potential roles in maintaining cardiac extracellular matrix integrity and ventricular function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "H Sumiyoshi, F Laub, H Yoshioka, et al. 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