Proprotein convertase subtilisin/kexin 9 (PCSK9) belongs to the proteinase K subfamily of subtilases and is expressed as a soluble zymogen that undergoes autocatalytic intramolecular processing in the endoplasmic reticulum. It is a 692 amino acid (aa) glycoprotein with an overall domain structure similar to other proprotein convertase members. It is comprised of a signal peptide (aa 1-30), a pro segment (aa 31-152), a catalytic domain (aa 153-407), a hinge region (aa 408-452), and a C-terminal Cys-His-rich domain (aa 453-692). The biological roles of PCSK9 are closely related to its binding partners, low-density lipoprotein (LDL) and LDL receptor (LDLR). At the cell surface, secreted PCSK9 binds at a neutral pH to the EGF-A-like repeat of the LDLR via its catalytic domain. The binding of PCSK9 to LDLR enhances the degradation of the LDLR in endosomes/lysosomes, which results in increased circulating LDL-cholesterol (LDL-C). Thus, PCSK9 has gained attention as a pharmacological target for cardiovascular diseases and atherosclerosis. It also binds to the Apoliprotein B (ApoB) in LDL, although its role in this complex is not clearly understood. Due to the interaction of PCSK9 with LDLR, the levels of free PCSK9 or its complexed forms are important indicators for measuring risk of cardiovascular diseases or response to a therapy.