Astrong inverse association exists between plasma HDL cholesterol (HDL-C) levels and incidence of coronary artery disease. 1 Although environmental factors play a role, variation in HDL-C levels are at least 50% genetically determined. 2 The genetics of syndromes of very low HDL-C have been extensively studied. Mutations in apoA-I (the major HDL structural protein), ABCA1 (which promotes efflux of cellular lipids to apoA-I forming nascent HDL particles), and LCAT (which converts unesterified cholesterol to cholesteryl ester [CE] to form the lipid core of mature HDL particles) have all been demonstrated to cause very low levels of HDL-C and apoA-I due to rapid catabolism of apoA-I. 3 However, their relationship to premature atherosclerosis is often uncertain, leading to the concept that the HDL-mediated “flux” of cholesterol from the periphery to the liver, where cholesterol is delivered for excretion into the bile (a process known as reverse cholesterol transport [RCT]), may be more important than the actual plasma concentrations of HDL-C in protecting against atherosclerosis.