The orphan nuclear receptors at their 25-year reunion

    1. Mitchell A Lazar
    1. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    1. Correspondence should be addressed to M A Lazar; Email: lazar{at}


    The nuclear receptor superfamily includes many receptors, identified based on their similarity to steroid hormone receptors but without a known ligand. The study of how these receptors are diversely regulated to interact with genomic regions to control a plethora of biological processes has provided critical insight into development, physiology, and the molecular pathology of disease. Here we provide a compendium of these so-called orphan receptors and focus on what has been learned about their modes of action, physiological functions, and therapeutic promise.

    • Revision received 3 October 2013
    • Accepted 4 October 2013
    • Made available online as an Accepted Preprint 4 October 2013
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