TBL1X (transducin beta like 1 X-linked) is an F-box-like protein that functions as a critical component of nuclear receptor corepressor complexes, particularly the NCOR1/SMRT complex 1. The protein plays an essential role in transcriptional regulation by recruiting the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units, facilitating the degradation of transcription repressor complexes and enabling cofactor exchange for transcriptional activation. TBL1X regulates multiple oncogenic signaling pathways including Wnt/β-catenin and NF-κB signaling 2. Beyond transcriptional control, TBL1X functions posttranscriptionally by promoting proteasomal degradation of oncoproteins through SCF/TBL1X supercomplex formation 2. The protein maintains genomic stability by controlling the stability of key proteins like cyclin D1 and RAD51, with its disruption leading to DNA damage and cell cycle arrest 3. TBL1X is overexpressed in various cancers and associated with poor prognosis 2. Clinically, TBL1X mutations cause X-linked central congenital hypothyroidism with hearing loss 41, though the protein's effects on thyroid hormone-regulated gene expression are gene-context dependent 1. TBL1X represents a promising therapeutic target, with small molecule inhibitors like tegavivint showing efficacy in preclinical cancer models 3.