What is the mechanism of action of PCSK9 inhibitors?

• A. Inhibits LDL receptor catabolism
• B. Inhibits HMG-CoA reductase
• C. Blocks cholesterol absorption in the intestine
• D. Activates LDL receptors directly

Answer: (A)

PCSK9 inhibitors work by preventing the PCSK9 protein from tagging LDL receptors for destruction. Normally, PCSK9 binds to LDL receptors on hepatocytes and directs them to lysosomes for degradation, reducing the number of receptors available to clear LDL cholesterol from the blood. When a PCSK9 inhibitor blocks this interaction, more LDL receptors are recycled back to the cell surface, increasing the liver’s capacity to remove LDL particles from circulation and lowering LDL cholesterol levels. This is why the mechanism is described as inhibition of LDL receptor catabolism. The other options describe mechanisms of different drug classes: statins inhibit HMG‑CoA reductase, ezetimibe blocks intestinal cholesterol absorption, and PCSK9 inhibitors do not directly activate receptors but increase their numbers by preventing degradation.