{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Laminin α5 (LAMA5) is a critical basement membrane component that not only provides structural integrity but also transduces signals essential for tissue development, homeostasis, and disease. In the skin, LAMA5-containing laminin‐10 is indispensable for hair follicle development by promoting proper basement membrane assembly and regulating key signaling pathways—including sonic hedgehog and Gli1—that drive follicle elongation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Likewise, at the neuromuscular junction, muscle‐derived laminin α5 facilitates postsynaptic maturation via the aggregation of dystroglycan."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the kidney, LAMA5 is essential for glomerular basement membrane formation and for mediating mesangial cell adhesion. Disruption in LAMA5 function impairs capillary loop convolution and contributes to polycystic kidney disease phenotypes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and increased transcription of LAMA5 has been linked to aberrant basement membrane thickening and permeability seen in Alport syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n During tooth development, laminin α5 directs the proliferation and polarization of dental epithelial cells, ensuring proper enamel knot formation and cusp patterning."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the developing lung, LAMA5 is required for alveolar epithelial differentiation and the production of VEGF, with its loss leading to dilated distal airspaces and incomplete lobar septation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond developmental roles, LAMA5 influences pathological processes. In breast cancer, tumor cells secrete abundant LAMA5, which engages in an autocrine loop with α3β1 integrin to support metastatic colonization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In KRAS‐mutant colorectal cancer hepatic metastasis, both tumor and stromal overexpression of LAMA5 mediates specific adhesion to endothelial cells, making the LAMA5/BCAM system a promising therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, endogenous LAMA5 is a key regulator of human pluripotent stem cell self‐renewal through autocrine signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and it helps maintain small intestinal mucosal architecture by influencing epithelial proliferation, migration, and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the multifunctional role of laminin α5 in orchestrating basement membrane structure and mediating cell–matrix interactions across diverse organ systems, with profound implications in normal morphogenesis and disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jie Li, Julia Tzu, Yi Chen, et al. 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