{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVPS13C encodes a large, evolutionarily conserved protein that acts as a lipid transporter at membrane contact sites. Structural and in situ cryo-electron studies reveal that its elongated, rod‐like conformation—with a continuous hydrophobic groove—enables it to shuttle glycerolipids between adjacent membranes such as the endoplasmic reticulum, late endosomes/lysosomes, and lipid droplets. This lipid transfer function is central to maintaining membrane lipid homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neuronal and other cellular contexts, loss‐of‐function mutations in VPS13C disrupt several aspects of organelle dynamics. In cell models, diminished VPS13C function is linked to altered lysosomal composition and impaired hydrolytic activity, reduced mitochondrial membrane potential, and increased mitochondrial fragmentation. Such disruptions contribute to enhanced mitophagy and an aberrant activation of innate immune signaling (via the cGAS–STING pathway), thereby establishing a mechanistic basis for its causal role in early‐onset Parkinson’s disease and related Lewy body disorders. Moreover, VPS13C’s interaction with key regulators such as Rab10 underscores its importance in maintaining proper lysosomal stress responses in neurons."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in neurodegeneration, VPS13C has been implicated in aspects of metabolic regulation. Genome‐wide association studies have linked VPS13C variants with altered 2‑hour post‐challenge glucose levels and insulin secretion, suggesting that it may influence glycemic traits. In line with this, proteomic investigations have identified VPS13C as a binding partner of TBC1D1—a key regulator of insulin- and exercise-stimulated GLUT4 trafficking—implying that VPS13C may also modulate insulin-responsive glucose uptake. Although the metabolic effects are modest and appear context-dependent, they highlight VPS13C’s multifaceted contributions to cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nikit Kumar, Marianna Leonzino, William Hancock-Cerutti, et al. 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