PCSK9: from molecular biology to clinical applications

Abstract

Proprotein convertase subtilisin kexin 9 (PCSK9) is a serine protease with a key role in regulating plasma low-density lipoprotein (LDL) concentration. Since its discovery via parallel molecular biology and clinical genetics studies in 2003, work to characterize PCSK9 has shed new light on the life-cycle of the low-density lipoprotein receptor and the molecular basis of familial hypercholesterolaemia. These discoveries have also led to the advent of the PCSK9 inhibitors, a new generation of low-density lipoprotein cholesterol (LDL-C) lowering drugs. Clinical trials have shown these agents to be both safe and capable of unprecedented reductions in LDL-C, and it is hoped they may herald a new era of cardiovascular disease prevention. As such, the still evolving PCSK9 story serves as a particularly successful example of translational medicine. This review provides a summary of the principal PCSK9 research findings, which underpin our current understanding of its function and clinical relevance.