PCSK9 function and physiology

During the past few years, the proprotein convertase subtilisin kexin 9 (PCSK9) field has been red hot, fueled by the realization that PCSK9 is a key player in plasma cholesterol metabolism and by a hope, shared by scientists in academia and industry alike, that PCSK9 is a target for treating hypercholesterolemia. PCSK9 regulates the levels of the LDL receptor (1–3), which is a plasma membrane glycoprotein that removes cholesterol-rich LDL particles from the plasma (4, 5). Gain-of-function mutations in PCSK9 reduce LDL receptor levels in the liver, resulting in high levels of LDL cholesterol in the plasma and increased susceptibility to coronary heart disease (6).