Extremely severe and ever-increasing hypercholesterolemia (total cholesterol up to 1,730 mg/dl) prompted an extensive search for causes of high GGT and/or hyperlipidemic cholestasis, including an extensive genetic liver panel (negative) and a liver biopsy showing a picture of obstructive cholangitis, biliary fibrosis, and bile duct proliferation with normal MDR3 protein expression. The gene discussed is ABCB4; the disease is cholestasis.