Image: Courtesy of David J. Mangelsdorf
 YIN AND YANG: Although they play opposite roles in bile acid production, these RXR heterodimers synergistically modulate cholesterol absorption and transport.

When the molecular basis of Tangier disease was discovered in 1999,1 researchers lined up to study this orphan genetic disorder. Patients with Tangier have a propensity for heart disease and atherosclerosis, making this rare malady a model for some pressing health problems found in industrialized nations. Following close behind the discovery of the Tangier gene were two studies, now deemed Hot Papers,2,3 that examined some of the molecular mechanisms upstream of the ATP-binding cassette A1 (ABCA1) involved in cholesterol transport and defective in patients with Tangier. One in vitro study demonstrated an orphan nuclear hormone receptor that senses the presence of cholesterol and turns on ABCA1.2 The second paper showed how molecules activating this gene and related pathways can...

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