Using animal models, it became clear that knockout of the Pcsk9 gene in mice results in a hypocholesterolemia phenotype with an 80% reduction in LDLc,67,68 an enhanced response to statins67, and a significant decrease in the development of atherosclerosis69 The reverse is observed in transgenic mice overexpressing the wild type form of PCSK9,69 or its D374Y GOF mutant,70 and in transgenic pigs expressing the D374Y mutant.71,72. This evidence concerns the gene PCSK9 and Hypocholesterolemia.