Cholesterol is one of the most important lipids in cells because of its crucial roles in maintaining cell viability and function. Cellular cholesterol is obtained from both de novo synthesis in the endoplasmic reticulum (ER) and by endocytosis of cholesterol containing ligands such as low-density lipoproteins (LDL). In normal cells, both newly synthesized and exogenously derived cholesterol redistribute in the cell to enrich pools of cholesterol in cell membranes, primarily the plasma membrane. Much of our knowledge of intracellular LDL derived cholesterol trafficking has been gained from studies of inherited metabolic diseases. Classic studies on familial hypercholesterolemia [1] illuminated the receptor mediated pathway for low-density lipoprotein-cholesterol delivery to lysosomes and cellular homeostatic regulation of low-density lipoprotein receptors, the rate limiting enzyme of de novo cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and the cholesterol esterifying enzyme, acyl-coenzyme A: cholesterol acyltransferase (ACAT). The role of lysosomes and cholesterol ester hydrolase in processing the cholesterol ester core of LDL emerged from studies of Wolmans syndrome