Rare mutations leading to reduced function of CETP have been linked to accelerated atherosclerosis. In contrast, a polymorphism (I405V) of the CETP gene leading to lower serum levels has also been linked to exceptional longevity  and to metabolic response to nutritional intervention. However, this mutation also increases the prevalence of coronary heart disease in patients with hypertriglyceridemia. The D442G mutation, which lowers CETP levels and increases HDL levels also increases coronary heart disease.
As HDL can alleviate atherosclerosis and other cardiovascular diseases, and certain disease states such as the metabolic syndrome feature low HDL, pharmacological inhibition of CETP is being studied as a method of improving HDL levels. To be specific, in a 2004 study, the small molecular agent torcetrapib was shown to increase HDL levels, alone and with a statin, and lower LDL when co-administered with a statin. Studies into cardiovascular endpoints, however, were largely disappointing. While they confirmed the change in lipid levels, most reported an increase in blood pressure, no change in atherosclerosis, and, in a trial of a combination of torcetrapib and atorvastatin, an increase in cardiovascular events and mortality.
A compound related to torcetrapib, Dalcetrapib (investigative name JTT-705/R1658), was also studied, but trials have ceased. It increases HDL levels by 30%, as compared to 60% by torcetrapib. Another CETP inhibitor under development is Merck's MK-0859 anacetrapib, which in initial studies did not increase blood pressure.
^Darabi M, Abolfathi AA, Noori M, Kazemi A, Ostadrahimi A, Rahimipour A et al. (2009). "Cholesteryl ester transfer protein I405V polymorphism influences apolipoprotein A-I response to a change in dietary fatty acid composition". Horm Metab Res41 (7): 554–8. doi:10.1055/s-0029-1192034. PMID19242900.
^Abbey M, Nestel PJ (March 1994). "Plasma cholesteryl ester transfer protein activity is increased when trans-elaidic acid is substituted for cis-oleic acid in the diet". Atherosclerosis106 (1): 99–107. doi:10.1016/0021-9150(94)90086-8. PMID8018112.
^Barter PJ, Brewer HB, Chapman MJ, Hennekens CH, Rader DJ, Tall AR (February 2003). "Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis". Arterioscler Thromb Vasc Biol23 (2): 160–7. doi:10.1161/01.ATV.0000054658.91146.64. PMID12588754.
^Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT et al. (March 2007). "Effect of torcetrapib on the progression of coronary atherosclerosis". N Engl J Med356 (13): 1304–16. doi:10.1056/NEJMoa070635. ISSN0028-4793. PMID17387129.
^Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ et al. (April 2007). "Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia". N Engl J Med356 (16): 1620–30. doi:10.1056/NEJMoa071359. PMID17387131.
Okajima F (March 2002). "[Distribution of sphingosine 1-phosphate in plasma lipoproteins and its role in the regulation of the vascular cell functions]". Tanpakushitsu Kakusan Koso47 (4 Suppl): 480–7. ISSN0039-9450. PMID11915346.
Dallinga-Thie GM, Dullaart RP, van Tol A (June 2007). "Concerted actions of cholesteryl ester transfer protein and phospholipid transfer protein in type 2 diabetes: effects of apolipoproteins". Curr. Opin. Lipidol.18 (3): 251–7. doi:10.1097/MOL.0b013e3280e12685. ISSN0957-9672. PMID17495597.