Chronicle of a discovery: the retinoic acid receptor

The landmark 1987 discovery of the retinoic acid receptor (RAR) came as a surprise, uncovering a genomic kinship between the fields of vitamin A biology and steroid receptors. This stunning breakthrough triggered a cascade of studies to deconstruct the roles played by the RAR and its natural and synthetic ligands in embryonic development, skin, growth, physiology, vision, and disease as well as providing a template to elucidate the molecular mechanisms by which nuclear receptors regulate gene expression. In this review, written from historic and personal perspectives, we highlight the milestones that led to the discovery of the RAR and the subsequent studies that enriched our knowledge of the molecular mechanisms by which a low-abundant dietary compound could be so essential to the generation and maintenance of life itself.