The membrane transporter ATP-binding cassette transporter Al (ABCAl) has been shown to be the rate-limiting step in the initial formation of plasma high-density lipoprotein (HDL) particles. The mechanisms of action of ABCAl, including its role in the vesicular transport of lipids to the cell surface for the lipidation of HDL apolipoproteins, are not fully understood. Niemann-Pick type C (NPC) disease is most often caused by mutations in the NPCl gene, whose protein product is believed to facilitate the egress of cholesterol and other lipids from late endosomes and lysosomes to other cellular compartments. This report reviews current knowledge regarding the role of ABCAl in vesicular lipid transport mechanisms required for HDL particle formation, and the relationship between ABCAl and NPCl in this process.