TBL1Y is a Y-linked gene encoding a transducin beta-like protein that functions as a transcriptional coregulator involved in nuclear receptor-mediated gene regulation. The protein acts as an F-box-like component of corepressor complexes, facilitating recruitment of the ubiquitin/19S proteasome complex to transcription units and enabling cofactor exchange through proteasomal degradation of repressor complexes 1. TBL1Y shows tissue-specific expression patterns, with notable expression in adult human cochlea, prostate, and during cardiac differentiation 23. Unlike its X-linked homolog TBL1X, TBL1Y demonstrates distinct functional properties and does not exhibit the same transcriptional repressor activity in reporter assays 4. The gene plays important roles in cardiovascular development, with knockdown studies showing reduced cardiac differentiation efficiency and impaired contractions, possibly through CtBP stabilization 3. Disease relevance includes association with Y-linked hereditary hearing loss, where missense variants cause protein instability and cellular dysfunction 2, and non-syndromic coarctation of the aorta, where functional null mutations disrupt protein stability 5. Additionally, specific TBL1Y haplotypes in individuals of African descent are associated with protective lipid profiles, potentially contributing to reduced coronary heart disease susceptibility 6.