PCSK9 (proprotein convertase subtilisin kexin 9), also known as NARC-1, is a member of the proteinase K subfamily of subtilisin-related serine endoproteases. It is highly expressed in the liver, intestine, and kidney and plays an important role in regulating LDL R expression and circulating cholesterol levels (1). PCSK9 is synthesized as precursor protein that is autocatalytically cleaved in the endoplasmic reticulum to generate a 14 kDa prodomain and a 60 kDa catalytic domain (2). Within the secretion pathway, the prodomain remains associated with and functions as a chaperone for the catalytic domain. Mouse PCSK9 shares 78% and 93% amino acid identity with human and rat PCSK9, respectively. PCSK9 plays a key role in the regulation of cholesterol metabolism by binding to hepatic LDL R, LRP-1, VLDL R, and Apolipoprotein E R2 and promoting their lysosomal degradation instead of recycling to the plasma membrane (3-8). It can also regulate cholesterol and triglyceride handling in the intestine and adipose tissue (9-11). The ability of PCSK9 to regulate LDL R expression is inhibited by its binding to LDL particles or Annexin A2 or by additional proteolytic cleavage (12-17).