{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nScavenger receptor class B type I (SCARB1) is a pivotal mediator in lipoprotein metabolism. It facilitates the selective uptake of cholesteryl esters from high‐density lipoprotein (HDL) into the liver and steroidogenic tissues, thereby promoting reverse cholesterol transport and impacting plasma lipid levels and atherosclerosis risk. Genetic and functional studies demonstrate that naturally occurring variants in SCARB1 can lead to paradoxical elevations in HDL cholesterol while increasing cardiovascular disease risk. In addition, SCARB1’s activity is regulated by accessory proteins such as PDZK1, which control its cell surface expression and recycling, and by naturally occurring splice variants (e.g., SR‐BII) that influence its intracellular trafficking and lipid sorting. These studies collectively underscore the receptor’s central role in maintaining cholesterol homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental role in lipid handling, SCARB1 serves as an essential host factor for viral infections. It mediates the entry of hepatitis C virus (HCV) by binding both viral envelope glycoproteins and associated host lipoproteins, thereby facilitating initial attachment and subsequent endocytosis in coordination with other co‐receptors like CD81. The receptor’s lipid transfer functions further enhance viral internalization and contribute to resistance against neutralizing antibodies. SCARB1 is also implicated in the cellular invasion of other pathogens, such as Plasmodium sporozoites, and plays a role in antigen uptake and cross‐presentation by dendritic cells, illustrating its diverse contribution to pathogen–host interactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSCARB1 further extends its ligand repertoire beyond traditional lipoproteins by mediating the uptake and signaling of various lipid‐soluble molecules. It contributes to the intestinal absorption of essential nutrients such as vitamin E and dietary carotenoids—including lutein, zeaxanthin, and lycopene—which are important for retinal and overall cellular health. In addition, SCARB1 binds inflammatory mediators like serum amyloid A and lipopolysaccharide, and it can directly recognize phosphatidylserine on apoptotic cells to promote phagocytic clearance. These diverse activities link SCARB1-mediated lipid transport with broader processes in immune regulation and inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of SCARB1 is emerging as a critical factor in various pathological conditions. Altered receptor function in endothelial cells has been linked to compromised cholesterol clearance and may contribute to atherosclerotic lesion development, while environmental stressors—such as cigarette smoke—can modify SCARB1 post‐translationally, disrupting skin cholesterol uptake. 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