{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATP‐binding cassette transporter G1 (ABCG1) is emerging as a key regulator of cellular cholesterol homeostasis by mediating the efflux of cholesterol—and in some cases oxysterols—from cells to lipidated high‐density lipoprotein (HDL) particles rather than to lipid‐poor apolipoproteins. ABCG1 is highly expressed in macrophages and other tissues where it functions either in concert with or subsequent to the action of ABCA1: the latter lipidates apoA‐I to generate nascent HDL particles that subsequently serve as acceptors for ABCG1‐mediated cholesterol export (see, for example."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition to promoting cholesterol efflux to both small (HDL3) and large (HDL2) HDL particles, overexpression studies and genetic knockdown models have revealed that ABCG1 significantly enhances macrophage reverse cholesterol transport and, when deficient, contributes to intracellular lipid accumulation and foam cell formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Mechanistic analyses indicate that ABCG1 operates by redistributing a pool of plasma membrane cholesterol—often from an oxidant‐sensitive domain accessible to cholesterol oxidase—to extracellular acceptors, a process that requires critical residues within its transmembrane domains."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, recent work suggests that ABCG1 predominantly localizes to intracellular compartments such as endosomes and is dynamically redistributed to the plasma membrane upon liver X receptor (LXR) activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Notably, ABCG1 also facilitates the efflux of oxysterols (e.g., 7‐ketocholesterol), thereby protecting macrophages from oxysterol‐induced cytotoxicity and inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings underscore the central role of ABCG1 in orchestrating cholesterol removal from cells, limiting lipid accumulation, and contributing to the anti‐atherogenic and anti‐inflammatory properties of HDL.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nan Wang, Debin Lan, Wengen Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0403506101"}], "href": "https://doi.org/10.1073/pnas.0403506101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15210959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15210959"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Matthew A Kennedy, Gabriel C Barrera, Kotoka Nakamura, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI32057"}], "href": "https://doi.org/10.1172/JCI32057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17657311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17657311"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Laurent Yvan-Charvet, Mollie Ranalletta, Nan Wang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "ABCA1 and ABCG1 synergize to mediate cholesterol export to apoA-I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000200082.58536.e1"}], "href": "https://doi.org/10.1161/01.ATV.0000200082.58536.e1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16357317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16357317"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ashley M Vaughan, John F Oram "}, {"type": "b", "children": [{"type": "t", "text": "ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M505368200"}], "href": "https://doi.org/10.1074/jbc.M505368200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15994327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15994327"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Elizabeth J Tarling, Peter A Edwards "}, {"type": "b", "children": [{"type": "t", "text": "ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1113021108"}], "href": "https://doi.org/10.1073/pnas.1113021108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22095132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22095132"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Nan Wang, Mollie Ranalletta, Fumihiko Matsuura, et al. 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