Multidrug resistance protein 3 (MDR3) (MDR3)

Multidrug resistance protein 3 (MDR3), encoded by the ABCB4 gene, is an ATP-binding cassette transporter primarily expressed on the canalicular membrane of hepatocytes (NIH, MedlinePlus). It functions as a phospholipid floppase, specifically translocating phosphatidylcholine from the inner to the outer leaflet of the membrane for secretion into the bile (UniProt, Wikipedia). This secretion is critical for the formation of mixed micelles, which sequester bile acids and protect the biliary tree from their detergent-like toxicity (NIH, ResearchGate). Genetic mutations in ABCB4 are associated with several liver disorders, including progressive familial intrahepatic cholestasis type 3 (PFIC3), intrahepatic cholestasis of pregnancy, and low phospholipid-associated cholelithiasis (MedlinePlus, NIH). Beyond its genetic roles, MDR3 is a significant target in pharmacology because its inhibition by various drugs, such as certain antifungals and antipsychotics, can lead to drug-induced liver injury (DILI) (NIH, PubMed). Therapeutic strategies currently focus on managing the resulting cholestasis with agents like ursodeoxycholic acid or developing chaperones to restore the function of mutant proteins (NIH, PatSnap). Understanding MDR3 activity is essential for predicting hepatotoxicity and developing treatments for chronic biliary diseases (NIH).

Other names

ABCB4ATP-binding cassette subfamily B member 4P-glycoprotein 3PGY3ABC21GBD1ICP3PFIC-3

Inhibition of canalicular phosphatidylcholine transport (NIH); alteration of biliary bile acid composition to reduce detergent toxicity (NIH); induction of transporter expression via FXR activation (NIH); stabilization of protein folding by pharmacological chaperones (NIH).