ABCB11 encodes the bile salt export pump (BSEP), an ATP-dependent transporter localized to the canalicular membrane of hepatocytes that catalyzes the secretion of conjugated bile salts, including taurine- and glycine-conjugated cholic acid, into bile 1. BSEP preferentially transports taurine-conjugated bile salts more rapidly than glycine-conjugated forms and also excretes non-bile acid compounds such as pravastatin and fexofenadine in an ATP-dependent manner 2. This transport function is essential for hepatic bile acid homeostasis and lipid metabolism regulation through control of biliary lipid secretion 1. BSEP deficiency, caused by biallelic ABCB11 mutations, results in progressive familial intrahepatic cholestasis type 2 (PFIC2), characterized by impaired bile flow, cholestasis, and intrahepatic accumulation of bile acids 3. Genotype severity correlates strongly with disease progression and native liver survival (median 20.4 years for BSEP1, 7.0 years for BSEP2, 3.5 years for BSEP3), and patients carrying protein-truncating mutations face significantly elevated hepatocellular carcinoma risk (38% versus 10%) 45. ABCB11 variants also associate with adult-onset pregnancy-related cholestasis and episodic cholestasis 6. Therapeutic strategies including surgical biliary diversion and ileal bile acid transporter inhibitors (maralixibat) improve pruritus and reduce serum bile acids, potentially modifying disease natural history 78.