ARV1 is a conserved eukaryotic protein that functions as a critical mediator of lipid homeostasis, particularly regulating cholesterol and phospholipid trafficking within cells. Mechanistically, ARV1 directly binds cholesterol and phospholipids through its conserved N-terminal ARV1 homology domain containing zinc-binding motifs, functioning as a lipid scramblase at the endoplasmic reticulum 1. ARV1 facilitates sterol transport from the ER to plasma membranes and regulates intracellular sterol distribution 2. Additionally, ARV1 acts as a functional component of the GPI N-acetylglucosaminyltransferase complex, enhancing recruitment of phosphatidylinositol to initiate glycosylphosphatidylinositol-anchor biosynthesis, thereby regulating GPI-anchored protein expression 3. ARV1 exists as a dimer, with oligomerization being essential for its lipid-binding and functional capacity 1. In disease, biallelic ARV1 mutations cause autosomal recessive developmental and epileptic encephalopathy 38 (DEE38), characterized by early-onset seizures, severe developmental delay, hypotonia, cerebellar atrophy, and impaired GPI-anchor synthesis 456. ARV1 deficiency represents a GPI-anchor synthesis disorder with neurological manifestations resembling inherited GPI deficiency disorders 5.