{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARV1 encodes an evolutionarily conserved transmembrane protein that localizes primarily to the endoplasmic reticulum (ER) and Golgi apparatus, where it plays multiple roles in lipid and membrane homeostasis. Studies in yeast have shown that deletion of ARV1 disrupts the normal distribution of sterols across cell membranes, alters sphingolipid and phospholipid metabolic flux, and leads to the accumulation of early sterol intermediates (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In mammalian systems, down‐regulation of ARV1 results in deficient neutral lipid synthesis, ER cholesterol accumulation, and perturbed bile acid metabolism, highlighting its critical function in intracellular sterol trafficking and regulation of lipid biosynthesis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Functional conservation is further underscored by the observation that human ARV1 can complement yeast ARV1 deficiencies—correcting defects not only in lipid metabolism but also in glycosylphosphatidylinositol (GPI) anchor synthesis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in lipid homeostasis, ARV1 has been implicated in other essential cellular processes. For example, its dynamic localization during the cell cycle and recruitment to the cleavage furrow during early telophase suggest a role in cytokinesis, where ARV1 helps recruit key contractile apparatus components (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Clinically, mutations or deficiencies in ARV1 are associated with severe phenotypes. In humans, ARV1 mutations have been linked to early-onset epileptic encephalopathy and disorders of GPI-anchor synthesis, which contribute to neurodevelopmental deficits (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ARV1 is a multifunctional protein crucial for maintaining lipid distribution and membrane composition by regulating the trafficking of sterols, sphingolipids, and GPI anchors, as well as contributing to proper cell division. Its pivotal functions in lipid metabolism and membrane dynamics make it essential for neuronal development and viability.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Evelyn Swain, Joseph Stukey, Virginia McDonough, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Yeast cells lacking the ARV1 gene harbor defects in sphingolipid metabolism. Complementation by human ARV1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M206624200"}], "href": "https://doi.org/10.1074/jbc.M206624200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12145310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12145310"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kelly V Ruggles, Jeanne Garbarino, Ying Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional, genome-wide evaluation of liposensitive yeast identifies the \"ARE2 required for viability\" (ARV1) gene product as a major component of eukaryotic fatty acid resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.515197"}], "href": "https://doi.org/10.1074/jbc.M113.515197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24273168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24273168"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Fumin Tong, Jeffrey Billheimer, Caryn F Shechtman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of ARV1 results in cholesterol retention in the endoplasmic reticulum and abnormal bile acid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.165761"}], "href": "https://doi.org/10.1074/jbc.M110.165761"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20663892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20663892"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Atsuko Ikeda, Kentaro Kajiwara, Kunihiko Iwamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complementation analysis reveals a potential role of human ARV1 in GPI anchor biosynthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Yeast (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/yea.3138"}], "href": "https://doi.org/10.1002/yea.3138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26460143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26460143"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hilde Sundvold, Vibeke Sundvold-Gjerstad, Helle Malerød-Fjeld, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Arv1 promotes cell division by recruiting IQGAP1 and myosin to the cleavage furrow."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2016.1146834"}], "href": "https://doi.org/10.1080/15384101.2016.1146834"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27104745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27104745"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Elizabeth E Palmer, Kelsey E Jarrett, Rani K Sachdev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw157"}], "href": "https://doi.org/10.1093/hmg/ddw157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27270415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27270415"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mariska Davids, Minal Menezes, Yiran Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous splice-variants in human ARV1 cause GPI-anchor synthesis deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2020.02.005"}], "href": "https://doi.org/10.1016/j.ymgme.2020.02.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32165008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32165008"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Reeval Segel, Adi Aran, Suleyman Gulsuner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A defect in GPI synthesis as a suggested mechanism for the role of ARV1 in intellectual disability and seizures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurogenetics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10048-020-00615-4"}], "href": "https://doi.org/10.1007/s10048-020-00615-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32462292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32462292"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Smrithi Salian, Marcello Scala, Thi Tuyet Mai Nguyen, et al. 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