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J Lipid Res. 2009 Apr;50 Suppl:S172-7. doi: 10.1194/jlr.R800091-JLR200. Epub 2008 Nov 19.

PCSK9: a convertase that coordinates LDL catabolism.

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  • 1Department of Internal Medicine, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.


The identification and characterization of proprotein convertase subtilisin-like/kexin type 9 (PCSK9) have provided new insights into LDL metabolism and the causal role of LDL in coronary heart disease (CHD). PCSK9 is a secreted protease that mediates degradation of the LDL receptor by interacting with the extracellular domain and targeting the receptor for degradation. Individuals with loss-of-function mutations in PCSK9 have reduced plasma levels of LDL cholesterol and are protected from CHD; these observations have validated PCSK9 as a therapeutic target and suggested new approaches for the treatment and prevention of CHD.

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