The hepatic uptake of LDL is highly regulated. The LDL receptor (LDL-R) present on hepatocytes mediates the endocytosis of LDL and thus regulates the plasma level of the lipoprotein and cholesterol. In the acidic environment of the endosome, the LDL-R dissociates from its ligand and recycles back to the cell surface for further uptake of LDL. Apo E is an alternate ligand for the LDL-R and mediates the clearance of triglyceride-rich lipoproteins such as chylomicron remnants and VLDL (2). ApoE also binds to additional hepatic receptors such as LDL-R related protein (LRP) and heparan sulfate proteoglycans (HSPG). Like apoE, Ac-hE18A-NH2 and its variants can reduce plasma cholesterol and displays anti-inflammatory properties in model animals. Ac-hE18A-NH2 has already undergone phase 1 clinical trials as a lipid-lowering agent. In a recent study, the myristyl peptide variant of ApoE has been shown to reduce total and LDL cholesterol (even under severe dyslipidemic conditions) in apoE-null mice. As a result, it is though myristyl can act as an alternative to statins and HMG-CoA reductase inhibitors. Additionally, because of its enhanced potency at lower doses, myristyl has great therapeutic potential to lower cholesterol.