Figure 1.

A, The role of PCSK9 in LDL receptor degradation and B, the mechanism of action of an anti‐PCSK9 antibody. PCSK9 binds to the receptor for LDL, and this complex is endocytosed and degraded intracellularly, thus reducing the number of available LDL receptors. Monoclonal antibodies targeted at PCSK9 can inhibit this interaction, by binding to circulating PCSK9 and thus facilitating the recycling of LDL receptors back to the cell surface. Therefore, the LDL‐receptors are made available to recognise and bind ApoB, a protein embedded in the phospholipid bilayer of LDL,13 the ApoB–LDL–LDL receptor complex is internalised and targeted for intracellular degradation, and thus LDL is removed from the circulation. ApoB, apoprotein B100; LDL, low‐density lipoprotein; LDLR, low‐density lipoprotein receptor; mAb, monoclonal antibody; PCSK9, proprotein convertase subtilisin/kexin type 9