Tangier disease is a rare recessive genetic disorder, char-acterized by extremely low HDL levels, accumulation of cholesterol esters in macrophages, and premature coronary heart disease. 1 The observation that fibroblasts from Tangier disease patients have a marked defect in efflux of cholesterol and phospholipids to apoA-I provided a key insight into the underlying defect. 2 Recently, 3 different groups made the exciting discovery that Tangier disease is caused by mutations in an adenosine triphosphate (ATP) binding cassette transporter, ABC1. 3–5 Thus, it is likely that ABC1 mediates or regulates the efflux of cellular cholesterol and phospholipids to apoA-I. Although ABC1 is widely expressed, the brunt of the defect is seen in macrophages, indicating their absolute dependence on an active cholesterol efflux pathway. The nature of the ABC1 molecule and the consequences of its mutation provide important evidence that reverse cholesterol transport underlies the atheroprotective effect of HDL. Already a multiplicity of ABC1 mutations have been described. 3–5 Importantly, heterozygous mutations can also cause the more common forms of familial hypoalphalipoproteinemia. 4