A role for phospholipid transfer protein (PLTP) in HDL remodelling and in the formation of pre-beta-HDL is now well established, both in vivo and in vitro. Over-expression of human PLTP in C57BL6 mice lowers plasma HDL levels, probably because of increased HDL catabolism. Despite these low HDL levels, plasma from these mice mitigates cholesterol accumulation in macrophages and has increased potential for pre-beta-HDL formation. Plasma HDL concentration is also decreased in PLTP knockout mice. These intriguing observations can be explained by recent studies that indicate that PLTP is not only involved in remodelling of HDL subfractions but also in VLDL turnover. The role of PLTP in atherogenesis and VLDL synthesis was demonstrated in transgenic mouse models with increased susceptibility for the development of atherosclerosis, bred into PLTP knockout mice. The data clearly show that PLTP can be proatherogenic. As mentioned above, however, PLTP may have antiatherogenic potential in wild-type C57BL6 mice. Information regarding the role and regulation of PLTP in human (patho)physiology is still relatively sparse but accumulating rapidly. PLTP activity is elevated in diabetes mellitus (both type 1 and type 2), obesity and insulin resistance.