Apolipoprotein A2 (Apo A2) is the second most abundant apolipoprotein in human plasma high-density lipoprotein (HDL), following Apo A1. It is the most hydrophilic protein among the exchangeable apolipoproteins. Apo A2 is synthesized by the liver and small intestine and exists in plasma as monomers or dimers. The Apo A2 gene consists of four exons and three introns. The four exons encode the 5′ untranslated region, signal peptide, a short N-terminal domain, and a C-terminal domain consisting of a variable number of lipid-binding amphipathic helices. Apo A2 stabilizes the structure of HDL by binding to lipids and influences HDL metabolism. The role of Apo A2 in lipid metabolism and atherosclerosis has important clinical significance. Apo A2 levels have been associated with susceptibility to atherosclerosis, increased levels of free fatty acids, body fat, and insulin resistance.