Cholesterol in the plasma membrane

Cholesterol is a rigid, amphipathic sterol molecule present in high abundance in animal plasma membranes—up to 40% of membrane lipids. It intercalates between phospholipids, aligning its hydrophobic rings and tail with fatty acid chains to modulate membrane fluidity: at physiological temperatures, cholesterol reduces membrane fluidity and permeability by stabilizing lipid packing; at lower temperatures, it increases fluidity by preventing phospholipid crystallization. Cholesterol also participates in the formation of lipid rafts, which are microdomains important for organizing membrane proteins and facilitating cell signaling processes. Its interaction with proteins, sphingolipids, and the cytoskeleton impacts receptor trafficking, signaling, and membrane fusion, with dysregulation implicated in diseases such as atherosclerosis and some neurodegenerative conditions. Cholesterol is not a protein, receptor, or classical drug target itself, but therapies affecting cholesterol transport and membrane concentration are crucial for disease management. Excessive alteration of cholesterol content can have significant safety and physiological consequences.

Other names

cholesterolmembranous cholesterolunesterified cholesterolmembrane cholesterol

Reduction of cholesterol biosynthesis (statins); Depletion/extraction of cholesterol from membranes (cyclodextrins); Inhibition of cholesterol absorption (ezetimibe)