Low-density lipoprotein (LDL) receptors expressed on hepatocytes mediate the removal of circulating LDL-cholesterol (LDL-C) from plasma via a receptor-mediated endocytic process. High circulating levels of LDL-C contributes to hypercholesterolemia, which is a known risk factor for cardiovascular disease.

The PCSK9 gene produces proprotein convertase subtilisin/kexin type 9 (neural apoptosis-regulated convertase 1, NARC1), an important regulator of plasma cholesterol homeostasis (Seidah et al. 2003). It binds to low-density lipoprotein receptor (LDLR) family members and promotes their degradation in intracellular acidic compartments (Poirer et al. 2008). This results in lower numbers of LDLRs on the surface of hepatocytes and as a consequence, circulating plasma levels of LDL-C are elevated.

The monoclonal antibodies alirocumab and evolocumab are approved PCSK9 inhibitor drugs for the treatment of familial hypercholesterolemia and dyslipidemias (Devito et al. 2015, Page & Watts 2015) . These antibodies bind PCSK9 on its catalytic site resulting in steric inhibition of binding between PCSK9 and LDL receptors (Duff et al. 2009).