Transducing ?-like protein 1 (TBL1X/TBL1) and TBL1-related protein 1 (TBL1XR1/TBLR1) were originally identified as subunits of the co-repressor silencing mediator for retinoic and thyroid hormone receptor (SMRT) and nuclear receptor co-repressor (NCoR) complexes . These two factors are required for the exchange of co-repressor complexes for co-activators by acting as adaptors to recruit the ubiquitin/proteasome machinery that degrades the co-repressor proteins during ligand mediated activation of transcription . Co-factor exchange driven by TBL1X/TBL1 and TBL1XR1/TBLR1 appears to be the mechanism by which c-Jun and NF-?B mediated transcription is activated and is therefore likely to be the mechanism employed by other signal-dependent transcription factors as well . In addition, both TBL1X/TBL1 and TBL1XR1/TBLR1 have essential roles in regulating the Wnt-signaling pathway by recruiting ?-catenin to Wnt target genes to activate transcription. Depletion of TBL1X-TBL1XR1 significantly inhibited Wnt-beta-catenin- induced gene expression and oncogenic growth in vitro and in vivo . Research studies have shown that upregulation of TBL1XR/TBLR1 is observed in a variety of solid tumors, and is correlated with advanced tumor stage, metastasis and poor prognosis.