Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 10 4 2020 08 09 PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD) 502 511 10.34172/apb.2020.062 EN Saeideh Sobati Amir Shakouri Mahdi Edalati Daryoush Mohammadnejad Reza Parvan Javad Masoumi Jalal Abdolalizadeh https://orcid.org/0000-0002-8283-5057 REVIEW 10.34172/apb.2020.062 2019 11 27 2020 02 02 Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-density lipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it binds to LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLR expression is adjusted at the transcriptional level through sterol regulatory element binding protein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and the inducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing the concentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, the effect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniques that focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 have been proposed which concentrate on both extracellular and intracellular PCSK9, and they include blockage of PCSK9 production by using gene silencing agents and blockage of it’s binding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tiny molecule inhibitors.