{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GBF1 (Golgi Brefeldin A Resistance Factor 1) is a pivotal guanine nucleotide exchange factor for Arf1 that orchestrates multiple facets of intracellular membrane trafficking. In its classic role, GBF1 promotes the formation of COPI‐coated vesicles and thus maintains Golgi architecture and cargo sorting. For example, GBF1 directly interacts with adipose triglyceride lipase (ATGL) through multiple contact sites—including its N‐terminal Sec7 domain and C‐terminal HDS domains—to facilitate the delivery of ATGL to lipid droplets, thereby linking vesicular trafficking to lipid metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " GBF1 activity is also finely regulated by post‐translational modifications; phosphorylation by AMP‐activated protein kinase (AMPK) during mitosis and under energy stress triggers GBF1 dissociation from Golgi membranes, leading to Golgi fragmentation and reorganization of secretory pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, lipolytic stimulation in skeletal muscle is associated with increased levels of GBF1, correlating with changes in lipid droplet‐associated proteins and suggesting a role in modulating lipid dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " GBF1 is also implicated in antiviral defense; its inhibition by the interferon‐induced protein viperin compromises proper viral particle assembly, thereby contributing to reduced virulence of certain flaviviruses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, pathogenic variants in GBF1 have been linked to distal hereditary motor neuropathies and axonal Charcot–Marie–Tooth disease, where defective GBF1 leads to Golgi fragmentation and impaired neuronal function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Advanced imaging and kinetic modeling studies have further revealed that GBF1 associates with Golgi membranes independently of Arf1 and that its regulation—partly via differential phosphorylation sites—is critical for proper COPI vesicle biogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, GBF1 contributes to the homeostatic control of plasma membrane tension by functioning within endocytic pathways modulated through mechanotransduction via vinculin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies underscore the multifaceted role of GBF1 as an essential regulator of Golgi structure, vesicle trafficking, lipid metabolism, and host defense mechanisms.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emy Njoh Ellong, Krishnakant G Soni, Quynh-Trang Bui, et al. 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