Proprotein Convertase Subtilisin / Kexin Type 9 Protein

Background

PCSK9 is a serine protease that plays a central role in cholesterol metabolism by regulating the levels of low-density lipoprotein receptors (LDLR) on the cell surface. PCSK9 binds to LDL receptors, promoting their internalization and subsequent degradation in lysosomes, which reduces the uptake of LDL cholesterol (LDL-C) from the bloodstream. Elevated PCSK9 activity leads to hypercholesterolemia and increases the risk of cardiovascular disease due to excessive circulating LDL-C levels. In contrast, loss-of-function mutations in PCSK9 result in reduced LDL receptor degradation, leading to low plasma cholesterol levels and decreased cardiovascular risk. PCSK9 inhibitors, such as monoclonal antibodies (e.g., alirocumab and evolocumab), are highly effective therapies for hypercholesterolemia and cardiovascular disease, as they block PCSK9's activity, preserving LDL receptors on cell surfaces to enhance cholesterol clearance. Beyond lipid metabolism, PCSK9 has been implicated in inflammation, immune regulation, and other pathological processes, making it a versatile target for therapeutic intervention. Its crucial role in cholesterol homeostasis underscores its significance in cardiovascular health and disease management.