{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC10A2, which encodes the apical sodium‐dependent bile acid transporter (ASBT), is a critical membrane protein that mediates the active, sodium‐coupled uptake of bile acids from the intestinal lumen. This transport activity ensures efficient enterohepatic recycling of bile acids and thereby maintains cholesterol homeostasis. In addition, its high substrate specificity has attracted interest as a target for prodrug design, and it plays a central role in several aspects of drug delivery by harnessing its efficient reabsorption of bile acids."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, the regulation and operational mechanisms of SLC10A2 are multifaceted. Genetic studies have identified sequence variants that affect its function and expression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and promoter analyses have revealed regulation by factors such as FXR, retinoic acid receptors, HNF1α, PPARα, and the intestinal transcription factors CDX1/2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, detailed topological and structural investigations confirm that ASBT adopts a 7‐transmembrane domain configuration with critical residues in specific extracellular loops and transmembrane segments ensuring substrate binding and sodium co‐transport."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": " Systematic mutagenesis and functional assays further underscore the importance of other regulatory elements and post‐translational modifications—such as precise N‐glycosylation, ubiquitination, tyrosine phosphorylation, and S‐acylation—in controlling membrane expression, oligomerization, and transport kinetics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, alterations in SLC10A2 function or expression—whether through genetic polymorphisms, post‐translational modifications, or regulatory dysregulation—have been linked to a spectrum of pathological conditions. Reduced SLC10A2 activity contributes to bile acid malabsorption in conditions such as gallstone disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": ", colorectal adenomas and cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": ", and familial hypertriglyceridemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": " Moreover, specific SLC10A2 haplotypes are associated with diminished ileal expression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": ", while altered transporter regulation in placenta or intestinal epithelia may impact conditions such as intrahepatic cholestasis of pregnancy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}]}, {"type": "t", "text": ", and the serum‐mediated transcriptional activation of its promoter further highlights potential endocrine influences."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "34"}]}, {"type": "t", "text": " In obesity, upregulation of ASBT enhances bile acid reabsorption and may contribute to the dyslipidemia underlying metabolic complications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "35", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ezequiel Neimark, Frank Chen, Xiaoping Li, et al. 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