CETP facilitates lipid exchange through a hetero-exchange mechanism, transferring CEs from HDL to apolipoprotein B (apoB)-containing lipoproteins (LDL and VLDL) while moving TGs in the opposite direction. Structurally, CETP features a boomerang-shaped molecule with a hydrophobic tunnel capable of binding two CEs and two phospholipids. The protein’s N- and C-terminal pockets interact with lipoprotein surfaces, enabling lipid transfer via a shuttle or tunnel model.

CETP’s activity modulates HDL-C and LDL-C levels, influencing reverse cholesterol transport (RCT), the process by which cholesterol is removed from peripheral tissues and delivered to the liver for excretion. Genetic deficiencies in CETP, observed in certain populations, result in elevated HDL-C and reduced LDL-C, correlating with lower cardiovascular risk in some cases. However, excessively high HDL-C levels may not always be protective, highlighting the complexity of CETP’s role. Assay kits designed to measure CETP activity provide researchers with robust tools to investigate its role in lipid homeostasis, evaluate CETP inhibitors, and explore its impact on metabolic disorders.

Applications in Lipid Metabolism Research

• Drug Development: CETP inhibitors, such as torcetrapib, dalcetrapib, evacetrapib, and obicetrapib, aim to increase HDL-C and reduce LDL-C to mitigate cardiovascular risk. Assay kits enable high-throughput screening of inhibitor efficacy. 
• Cardiovascular Disease Studies: CETP activity correlates with atherogenic lipid profiles. Assay kits have been used to study CETP’s role in heart failure, where reduced CETP levels in severe cases (NYHA class III/IV) were associated with lower total cholesterol and LDL-C. These findings suggest CETP as a biomarker for disease severity.
• Neurological and Metabolic Disorders: Emerging evidence links CETP to Alzheimer’s disease and diabetes. CETP transgenic mice exhibit altered brain cholesterol levels, potentially affecting cognitive function. Assay kits facilitate studies of CETP’s impact on cholesterol distribution in the central nervous system. In diabetes, CETP inhibitors like dalcetrapib reduce new-onset diabetes risk, a finding supported by assay-based studies of lipid transfer dynamics.
• Genetic and Nutritional Studies: CETP polymorphisms, such as D442G, influence HDL-C levels. Assay kits have been used to assess CETP activity in populations with genetic variants, revealing higher HDL-C in D442G carriers. Nutritional interventions, such as kiwifruit consumption, modulate CETP expression, as shown in hamster studies using assay kits.