HDL has a key role in reverse cholesterol transport, mobilizing cholesterol from the peripheral tissues to liver. In this process, the ABC transporter A1 (ABCA1) protein controls the efflux of intracellular cholesterol to apoAI, the major apolipoprotein of HDL. Since ABCA1 mutations were discovered to cause Tangier disease, a rare recessive HDL deficiency, it has been speculated that sequence variants in ABCA1 might also contribute to variations in plasma HDL cholesterol levels in the general population. A new study provides genetic evidence supporting this hypothesis.