Background: TBLR1 is a six WD-40 repeat protein with high sequence homology to TBL1 (transducin beta-like protein 1) and is part of the SMRT (silencing mediator of retinoid and thyroid hormone receptors) and N-CoR (nuclear receptor corepressor) complexes that interact with nuclear receptors and repress transcription. Biochemical characterization of SMRT and N-CoR complexes demonstrate that SMRT and N-CoR are present in complexes that include HDAC3 (histone deacetylase 3), TBL1, and TBLR1. Association with HDAC3 indicates that these complexes may repress transcription through histone deacetylation and chromatin remodeling.