Cholesterol is an essential component of cell barrier formation and signaling transduction involved in many essential physiologic processes. Cholesterol is an essential component of cell barrier formation and cell signaling transduction that regulates membrane fluidity and interacts with other lipids and proteins.Cholesterol can also regulate the function of many proteins, directly by interacting with them  or indirectly by its effects on membrane fluidity. Among cholesterol interacting proteins are proteins accepting cholesterol as a substrate (Acyl-CoA acyl-transferase (ACAT)), proteins that need cholesterol-rich environments to effectively interact with the membrane (cholesterol-dependent cytolysins), proteins with sterol binding domains (cleavage-activating protein (SCAP)) or hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) [8,9], proteins with cholesterol recognition amino acids consensus’ (CRAC) domain and many others.
In the recent past, several studies have been conducted to test the lipid-lowering activity derived by the inhibition of a serine protease, the proprotein convertase subtilisin/kexin type 9 (PCSK9), able to promote degradation of liver LDL receptors. This mechanism of action has been thought to be a successful strategy to manage hypercholesterolemia, in particular in subjects intolerant to statins and/or affected by serious genetic dysfunctions such as Homozygous and Heterozygous Familial Hypercholesterolemia (HoFH and HeFH), and/or very far from their LDL-C target based on the individual CV risk.1.Asier Benito-Vicente,et al. Int. J. Mol. Sci. 2018, 19, 3426.