Cholesterol is an essential component of eukaryotic membranes. To prevent the toxicity associated with cholesterol overload, cells transport excess cholesterol across the plasma membrane in part through the ABCA1 lipid transporter. The discovery that mutations in ABCA1 are associated with high-density lipoprotein (HDL)-deficiency syndromes led to studies that show ABCA1, through its transport of cholesterol and phospholipid to apolipoprotein acceptors in the bloodstream, is crucial for the formation of HDL particles. In the intestine, ABCA1 transports cholesterol from the epithelial cells to the bloodstream, contributing to approximately one-third of HDL production. In the arterial wall, excess cholesterol in macrophages is associated with atherosclerosis; here, ABCA1 is anti-atherogenic because it enables macrophages to rid themselves of excess cholesterol.