ABCB11

ABCB11, also known as the bile salt export pump (BSEP), is a gene encoding a member of the ATP-binding cassette (ABC) transporter family. The protein is expressed in hepatocytes and localizes to the canalicular (bile-facing) membrane, where it functions as a transporter involved in bile formation.

BSEP uses energy from ATP hydrolysis to actively efflux bile acids from hepatocytes into the bile canaliculi. It transports a broad range of primary and secondary bile acids and their conjugates, contributing to the enterohepatic circulation and shaping bile composition. By removing bile acids from liver cells, BSEP helps protect hepatocytes from bile acid–induced toxicity and supports the digestive process.

Regulation of ABCB11 expression is linked to bile acid signaling. Farnesoid X receptor (FXR) activation, triggered by elevated bile acids, upregulates ABCB11 transcription, increasing BSEP levels at the canalicular membrane. This regulatory axis forms part of a feedback mechanism that maintains bile acid homeostasis.

Clinical significance varies with genetic and functional status of BSEP. Mutations in ABCB11 cause progressive familial intrahepatic cholestasis type 2 (PFIC2), a severe liver disorder characterized by impaired bile flow and cholestasis that can present in infancy or early childhood. Heterozygous or partial loss-of-function variants can contribute to cholestatic phenotypes in some individuals. BSEP dysfunction is also implicated in drug-induced cholestasis and, in some cases, intrahepatic cholestasis of pregnancy, where altered transporter activity may exacerbate maternal or fetal liver injury.

In research and medicine, ABCB11 remains a focus for understanding bile acid homeostasis, cholestasis mechanisms, and potential therapeutic approaches to enhance or restore BSEP function.