Vacuolar protein sorting-associated protein 13A (VPS13A)

Vacuolar protein sorting-associated protein 13A (VPS13A) is a very large, multi-domain lipid transfer protein found primarily at membrane contact sites between the endoplasmic reticulum, mitochondria, and lipid droplets[1][2][3]. It establishes inter-organelle connections, especially between the ER and mitochondria, through its FFAT motif binding to VAP-A/B and its C-terminal anchoring to the mitochondrial outer membrane[1][3]. VPS13A contains several structural domains, including an N-terminal chorein domain critical for actin cytoskeleton regulation, a lipid-binding domain for lipid shuttling, HEAT repeats, and a C-terminal pleckstrin homology (PH) domain[2][3]. Its evolutionarily conserved function is the bulk transfer of lipids between bilayers, which is essential for proper organelle function and membrane biogenesis. Loss-of-function mutations in the VPS13A gene result in Chorea-acanthocytosis, a severe neurodegenerative disease characterized by movement disorders (chorea), red blood cell abnormalities (acanthocytosis), and progressive neurodegeneration[1][2]. There are no known drugs that directly target VPS13A, but the protein is of interest for future therapeutic targeting due to its central role in organelle biology and implication in rare inherited diseases[1][3].

Other names

Intermembrane lipid transfer protein VPS13AChoreinChorea-acanthocytosis proteinBridge-like lipid transfer protein family member 5ABLTP5ACHACKIAA0986Vacuolar protein sorting 13 homolog AVacuolar protein sorting 13A