PCSK9: from biology to clinical applications

Summary Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial protein governing the circulating levels of low density lipoprotein-cholesterol (LDL-C), by virtue of its pivotal role in the degradation of the LDL receptor (LDLR). In the last 15 years, in vitro and in vivo studies have allowed our understanding of the physiological role of PCSK9. In the current report, we review the key studies that have established the mode of action of PCSK9, leading to the development of PCSK9 inhibitors for clinical use. Data from clinical trials investigating these therapies clearly and unambiguously demonstrate the safety and efficacy of these new drugs that have the power to dramatically reduce LDL-C and associated cardiovascular diseases.