Absorption of dietary cholesterol from the intestine is an important part of cholesterol homeostasis and represents the initial step that allows dietary cholesterol to exert its metabolic effects. A typical western diet contains relatively equal amounts of cholesterol and non-cholesterol sterols, mainly plant sterols, of which about 55% of the dietary cholesterol is absorbed and retained compared to ~1% of the dietary non-cholesterol sterols [1-3]. Schoenheimer recognized more than 75 years ago that only cholesterol, not non-cholesterol sterols, is absorbed in the intestine, although the exact molecular mechanisms by which preferential cholesterol absorption occurs has not been fully elucidated [4]. Similarly, although the liver secretes free cholesterol into bile, it can preferentially excrete non-cholesterol sterols into bile and the mechanism(s) of this process has yet to be elucidated as well. Only recently, through the study of a rare human disease, have clues to this process been revealed.