Cholesterol ester transfer protein: a molecule with three faces?

The pathogenesis of atherosclerosis continues to be a focus of intensive study. One of the more recent players in the atherosclerosis drama is cholesterol ester transfer protein (CETP). CETP is primarily involved in lipid transfer between lipoproteins, for example, from high-density lipoproteins (HDL) to apo B-containing lipoproteins, but CETP has also been found to take up cholesterol directly from cells without the co-participation of lipoproteins, and it is still not clear whether CETP should be classified as a beneficial or as a harmful protein. Some of the important evidence for these conflicting theories is examined here, with special reference to situations where CETP appears to be proatherogenic, instances where CETP seems to assume an antiatherogenic role, and situations where CETP seems to be both proatherogenic and antiatherogenic. In addition, the metabolic context of CETP and the modification of CETP substrates play crucial roles that are not always recognized when judgements about the role of CETP in atherosclerosis are recorded.