Cosa fa questo gene
Liver cells pull LDL cholesterol out of the blood using receptors on their surface. PCSK9 destroys those receptors, so more cholesterol stays in circulation. People born with a broken PCSK9 gene have low cholesterol and appear entirely healthy — which is exactly why it is such an attractive target: nature has already run the experiment.
PCSK9, at 1p32.3, encodes a protease that binds the LDL receptor and directs it to lysosomal degradation, reducing hepatic LDL clearance. Loss-of-function variants are associated with lifelong low LDL cholesterol and reduced cardiovascular events without evident harm; gain-of-function variants cause familial hypercholesterolemia. It is validated as a drug target by approved monoclonal antibodies and siRNA medicines, and is the target of in vivo base-editing programmes intended to make the effect permanent.
Sources
- New England Journal of Medicine (Cohen et al.) · 2006
Sequence variations in PCSK9, low LDL, and protection against coronary heart disease ↗