Description
PCSK9 (also known as neural apoptosis-regulation convertase, NARC-1) is a 692-residue extracellular protein expressed primarily in the kidneys, liver and intestines representing the 9th member of the secretory subtilase family. Various genetic observations subsequently mapped PCSK9 as the third gene (along with LDLR and APOB) to cause autosomal dominant hypercholesterolemia (ADH). These studies suggested that gain of function mutations increase plasma levels of LDL-c, whereas nonsense or missense (loss-of-function) mutations, which interfere with folding or secretion of coronary heart disease (CHD). In mice, adenoviral overexpression of PCSK9 results in increased plasma LDL-c level in normal mice but not in LDLR-deficient mice. Deletion of PCSK9 causes an increase in level of LDLR protein but not mRNA.These findings lead to a hypothesis that PCSK9 exerts its role in cholesterol metabolism through posttranslational down-regulation of LDLR, the receptor responsible for clearing LDL-c from plasma