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Proprotein convertase subtilisin/kexin type 9 and lipid metabolism

Spolitu, Stefano; Dai, Wen; Zadroga, John A.; Ozcan, Lale

Current Opinion in Lipidology: June 2019 - Volume 30 - Issue 3 - p 186–191
doi: 10.1097/MOL.0000000000000601
LIPID METABOLISM: Edited by Marit Westerterp and Bart van de Sluis

Purpose of review The purpose of this review is to highlight the recent findings of one of the most promising therapeutic targets in LDL cholesterol (LDL-C) management, proprotein convertase subtilisin/kexin type 9 (PCSK9).

Recent findings Endoplasmic reticulum cargo receptor, surfeit locus protein 4 interacts with PCSK9 and regulates its exit from endoplasmic reticulum and its secretion. Once secreted, PCSK9 binds to heparin sulfate proteoglycans on the hepatocyte surface and this binding is required for PCSK9–LDL receptor (LDLR) complex formation and LDLR degradation. Posttranscriptionally, recent work has shown that PCSK9 gets degraded in lysosomes by activation of the glucagon receptor signaling, providing more data on the hormonal regulation of PCSK9. Finally, human studies with PCSK9 inhibitors offered more evidence on their benefits and safe use.

Summary Recent work on the regulation of PCSK9 has enhanced our understanding of its biology, which may provide important information for future PCSK9-based therapies.

Department of Medicine, Columbia University, New York, New York, USA

Correspondence to Lale Ozcan, Department of Medicine, Columbia University, 630 West 168th Street, Black Building, 9th Floor, Room: 901D, New York, NY 10032, USA. Tel: +1 212 305 7909; e-mail:

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