{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ABCG4 is a half‐type ATP‐binding cassette transporter that is predominantly expressed in the central nervous system – notably in neurons and microglia – and plays a multifaceted role in regulating sterol homeostasis. Studies in transfected cells have demonstrated that, similar to its close homolog ABCG1, ABCG4 promotes the efflux of cholesterol to high‐density lipoproteins, thereby protecting cells from cholesterol overload."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In vivo analyses further reveal that ABCG4 contributes to the intracellular trafficking of cholesterol within vesicular compartments in neurons and astrocytes, coordinating the organization of membrane lipid microdomains. This activity has been linked to modulation of amyloid precursor protein processing and a reduction in amyloid‐β secretion, which is particularly relevant to Alzheimer’s disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, ABCG4 forms functional homodimers and can also heterodimerize with ABCG1, suggesting an element of cooperative regulation that may extend to influencing apoptosis in certain contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Its protein levels and, consequently, its activity in promoting cholesterol efflux are tightly controlled by post‐translational modifications; for instance, specific E3 ubiquitin ligases have been shown to regulate ABCG4 degradation, thereby modulating its cellular function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, evidence from biochemical fractionation studies indicates that ABCG4 is enriched in specific plasma membrane meso‐domains distinct from those occupied by related transporters—a feature that may influence the extraction and redistribution of cellular sterol pools."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its canonical role in lipid export, ABCG4 has been implicated in the clearance of neurotoxic amyloid‐β peptides at the blood–brain and blood–cerebrospinal fluid barriers, thereby contributing to the maintenance of neural tissue integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, recent reports have identified an association between ABCG4 expression and chemoresistance in cancer cell models, wherein its induction facilitates the efflux of chemotherapeutic agents and is linked to unfavorable clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the versatility of ABCG4 as a regulator of both intracellular and extracellular sterol transport. By mediating cholesterol efflux, reorganizing membrane lipid architecture, and influencing amyloid metabolism and drug transport, ABCG4 plays a critical role in lipid homeostasis within the brain and may represent a potential target for therapeutic intervention in neurodegenerative disorders and cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nan Wang, Debin Lan, Wengen Chen, et al. 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