Ileal bile acid transporter (IBAT) (IBAT)

The ileal bile acid transporter (IBAT), also known as the apical sodium-dependent bile acid transporter (ASBT), is a transmembrane protein encoded by the SLC10A2 gene that mediates the first and rate-limiting step of the enterohepatic circulation of bile acids [UniProt: P41163]. It is primarily localized to the apical membrane of enterocytes in the distal ileum, where it facilitates the sodium-dependent uptake of conjugated bile acids from the intestinal lumen [PubMed: 25613007]. By reclaiming approximately 95% of secreted bile acids, IBAT maintains the systemic bile acid pool and regulates hepatic bile acid synthesis via feedback mechanisms involving the farnesoid X receptor (FXR) and fibroblast growth factor 19 (FGF19) [PubMed: 31054165]. Dysregulation or genetic mutations in SLC10A2 are associated with primary bile acid malabsorption, while its pharmacological inhibition has emerged as a key strategy for treating cholestatic liver diseases [PubMed: 34289463]. IBAT inhibitors, such as odevixibat and maralixibat, work by blocking bile acid reabsorption, thereby reducing the toxic accumulation of bile acids in the liver and blood, which significantly alleviates symptoms like severe pruritus [FDA: Livmarli, Bylvay]. Beyond cholestasis, IBAT is a target for treating chronic idiopathic constipation and is being investigated for metabolic conditions like nonalcoholic steatohepatitis (NASH) and type 2 diabetes due to its influence on glucose and lipid metabolism [PubMed: 28438694].

Other names

Apical sodium-dependent bile acid transporterASBTSolute carrier family 10 member 2SLC10A2Sodium/bile acid cotransporterNTCP2

Inhibition of the apical sodium-dependent bile acid transporter in the terminal ileum, preventing the reabsorption of bile acids and increasing their fecal excretion.