Atherosclerosis and associated CVD remains the largest cause of mortality worldwide (1). Despite substantial benefit offered by statin monotherapy, cardiovascular events still claim more lives than any other cause. To address this unmet therapeutic need, drug discovery efforts have shifted toward novel approaches to alter cholesterol metabolism that do not rely on inhibition of cholesterol synthesis. Elevation of HDL cholesterol has been a popular therapeutic strategy (2). However, recent clinical trials (3,4) have failed to show clinical benefits of HDL cholesterol elevation, and Mendelian randomization studies question the causal link between HDL cholesterol levels and CVD (5).