lipid.siteThe liver, LDL receptors and PCSK9
Your LDL level is mostly a balance: how much LDL your liver sends out, and how fast its receptors pull LDL back in.
Your liver clears LDL
LDL particles carry cholesterol in your blood. The liver pulls them out using LDL receptors, like hooks on its surface. Each receptor grabs a particle, pulls it inside, and comes back up for another.
Key takeaways
- 1
Your liver pulls LDL out of the blood with LDL receptors, like hooks on its surface. Each receptor grabs a particle, pulls it inside, and comes back up for another.
- 2
PCSK9 is a protein that latches onto a receptor. Instead of coming back up, that receptor gets destroyed. Fewer receptors means more LDL stays in the blood.
- 3
When a liver cell runs low on cholesterol, it switches on more receptors. Several medicines work by sending exactly that signal.
Go deeper
▸Inside the liver cell
Inside, the receptor drops its LDL at a sorting station (the endosome) and rides back to the surface to be used again, hundreds of times. The LDL goes on to the lysosome, the cell's recycling bin, which frees its cholesterol for the cell to use.
Receptors that arrive with PCSK9 attached are sent to the lysosome too, and destroyed instead of recycled.
▸How the cell decides how many receptors to make
The cell senses how much cholesterol it has. When it runs low, a switch called SREBP-2 turns up the LDL receptor gene. Statins and bempedoic acid work this way: they slow the cell's own cholesterol making, so it builds more receptors.
▸When the genes are different
In familial hypercholesterolemia (FH), a gene change means LDL is cleared poorly from birth, often because the liver has fewer working receptors. It affects about 1 in 250 people and runs in families.
Some people are born with PCSK9 that doesn't work. They have low LDL for life and less heart disease, a finding that helped make PCSK9 a target for medicines.
What people experienced
One person's experience isn't a prediction of yours.
Sources
- Familial hypercholesterolemia, MedlinePlus Genetics (NIH)
- Familial hypercholesterolemia and Lp(a), Family Heart Foundation
- Cholesterol, American Heart Association
- National Lipid Association, National Lipid Association
Not medical advice. This exhibit is general education to help you understand your condition and talk with your clinician. It doesn't tell you what to take or change. If you have chest pain or other signs of a heart attack or stroke, call 911.
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