Estrogen-related Receptor β (ERRβ) – Renaissance Receptor or Receptor Renaissance?

Estrogen-related receptors (ERRs) are founding members of the orphan nuclear receptor (ONR) subgroup of the nuclear receptor superfamily. Twenty-seven years of study have yet to identify cognate ligands for the ERRs, though they have firmly placed ERRα (ESRRA) and ERRγ (ESRRG) at the intersection of cellular metabolism and oncogenesis. The pace of discovery for novel functions of ERRβ (ESRRB), however, has until recently been somewhat slower than that of its family members. ERRβ has also been largely ignored in summaries and perspectives of the ONR literature. Here, we provide an overview of established and emerging knowledge of ERRβ in mouse, man, and other species, highlighting unique aspects of ERRβ biology that set it apart from the other two estrogen-related receptors, with a focus on the impact of alternative splicing on the structure and function of this receptor.