A decade after our discovery of the involvement of proprotein convertase 
subtilisin/kexin type 9 (PCSK9) in cholesterol metabolism through the 
identification of the first mutations leading to hypercholesterolemia, PCSK9 has 
become one of the most promising targets in cholesterol and cardiovascular 
diseases. This challenging work in the genetics of hypercholesterolemia paved 
the way for a plethora of studies around the world allowing the characterization 
of PCSK9, its expression, its impact on reducing the abundance of LDL receptor, 
and the identification of loss-of-function mutations in hypocholesterolemia. We 
highlight the different steps of this adventure and review the published 
clinical trials especially those with the anti-PCSK9 antibodies evolocumab (AMG 
145) and alirocumab (SAR236553/REGN727), which are in phase III trials. The 
promising results in lowering LDL cholesterol levels raise hope that the PCSK9 
adventure will lead, after the large and long-term ongoing phase III studies 
evaluating efficacy and safety, to a new anticholesterol pharmacological class.