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Updated: Apr 14, 2026
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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
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Role of PCSK9 beyond liver involvement
Bertrand Cariou1, Karim Si-Tayeb, Cédric Le May
1aInserm, UMR1087-CNRS UMR6291, l'Institut du Thorax bUniversité de Nantes, Faculté de Médecine, Institut du Thorax cDepartment of Endocrinology, l'Institut du Thorax, University Hospital of Nantes, Nantes, France.
Current Opinion in Lipidology
|April 19, 2015
Summary
Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates cholesterol. While known for liver function, PCSK9 also impacts intestinal lipid metabolism and potentially other organs, requiring further research.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of the low-density lipoprotein (LDL) receptor pathway.
- PCSK9 targets LDL receptors for lysosomal degradation, influencing cholesterol homeostasis.
- PCSK9 is expressed in various tissues beyond the liver, with its extrahepatic functions largely unexplored.
Purpose of the Study:
- To review the extrahepatic actions of PCSK9.
- To elucidate the role of PCSK9 in non-hepatic tissues and its implications for lipid and glucose metabolism.
Main Methods:
- Review of existing literature and studies.
- Analysis of data from liver-specific PCSK9 knockout mice.
- Examination of genetic and pharmacological approaches.
Main Results:
- PCSK9 significantly influences cholesterol homeostasis through extrahepatic organs, particularly the intestine.
- Intestinal PCSK9 regulates triglyceride-rich lipoprotein production and transintestinal cholesterol excretion.
- The role of PCSK9 in the pancreas, kidneys, vascular smooth muscle, and neurons remains under investigation due to conflicting or sparse data.
Conclusions:
- Intestinal PCSK9 plays a crucial role in modulating lipid homeostasis.
- Further research is needed to fully understand PCSK9's physiological functions in extrahepatic tissues.
- Deciphering these functions is essential for assessing the safety of PCSK9 inhibitors.
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