Phospholipid transfer protein (PLTP; also known as lipid transfer protein II) is an 80 kDa, secreted glycoprotein, that belongs to the BPI/LBP/Plunc superfamily of molecules. It is synthesized as a precursor with a 17 amino acid (aa) signal sequence and a 476 aa mature chain. The mature chain contains two BPI/LBP/CETP domains (aa 21-239 and 263-463) and seven potential sites for N-linked glycosylation. Mature mouse PLTP shares 83% aa sequence identity with mature human PLTP. PLTP is expressed by a wide variety of tissues and is secreted by macrophages. Northern blot analysis shows the order of PLTP mRNA expression as follows: lung, adipose tissue, placenta, testis, brain, muscle, heart, liver. PLTP is a multifunctional, extracellular lipid transfer protein that plays a major role in lipoprotein metabolism and atherosclerosis. In addition to phospholipids, PLTP transfers several amphipatic compounds, including unesterified cholesterol, lipopolysaccharides, diacylglycerides, and alpha-tocopherol, the main isomer of vitamin E. According to several studies, PLTP not only affects plasma lipid and lipoprotein profiles, but also modulates cell physiology. In mice, systemic PLTP deficiency proves to be atheroprotective, whereas PLTP overexpression is proatherogenic. However, macrophage PLTP is shown to be atheroprotective.