Figure 1.

The role of PCSK9 in lipoprotein metabolism. The expression of LDLR and PCSK9 are regulated by SREBP-2. The PCSK9 secreted from the endoplasmic reticulum to the Golgi apparatus, and then from trans-Golgi network into the medium. It can be sorted directly to lysosomes as a complex with the LDLR (intracellular pathway), or secreted into the plasma and then internalized with the LDLR into clathrin-coated endosomes for lysosomal degradation (Extracellular pathway). Both mechanisms result in the reduction of LDLR, and then LDL clearance from the circulation is reduced.; LDL-R, LDL receptor; SREBP-2, Sterol regulatory element-binding protein-2; HMG-CoA, 3-hydroxy-3methylglutaryl coenzyme A.