The two major isoforms of thyroid hormone receptor, TRα1 and TRβ1, preferentially partner with distinct panels of auxiliary proteins

•Thyroid hormone receptors (TRs) are synthesized primarily as two isoforms, α1 and β1.•LC–MS/MS was used to identify potential TRα1-selective versus TRα1 and TRβ1 coregulators.•A subset of coregulator candidates were selectively recruited by TRα1 compared to TRβ1.•Our results may help explain the distinct transcription properties of TRα1 and TRβ1. Thyroid hormone receptors (TRs) are expressed primarily as two major isoforms, TRα1 and TRβ1, which are expressed at different times in development and at different tissue abundances in the adult. The transcription properties and biological properties of TRα1 and TRβ1 can differ. We report here that although overlapping, TRα1 and TRβ1 recruit distinct panels of partner proteins that may account for their divergent biological functions, and which appear to explain their distinct target gene regulatory properties.