TLE3 is a transcriptional corepressor that functions as a critical regulator of cell lineage identity and differentiation across multiple tissues. In adipogenesis, TLE3 acts as a corepressor of Wnt signaling by inhibiting transcriptional activation mediated by CTNNB1 and TCF family members, while simultaneously serving as a coactivator for PPARG to promote white adipocyte differentiation 1. TLE3 also prevents white adipose tissue browning by blocking the association between PRDM16 and PPARG. In breast cancer, TLE3 sustains luminal cell fate by repressing genes associated with basal-like phenotypes, including SOX9 and TGFβ2, thereby preventing epithelial-mesenchymal transition and metastatic progression 2. Conversely, TLE3 suppression via miR-3677 upregulation promotes breast cancer cell proliferation, migration, and invasion 3. In skeletal muscle, TLE3 functions upstream of Zeb1 to regulate myogenic differentiation, controlling both transcriptional and post-transcriptional mechanisms of myosin heavy chain-embryonic expression 4. TLE3 protein stability is regulated by TRIM56-mediated K48-linked ubiquitination, with TLE3 degradation promoting thermogenic gene activation and white adipose tissue browning 5. TLE3 expression is glucocorticoid-responsive in the brain 6, and genetic variants in TLE3 have been associated with neuropathological severity in Lewy body disease 7.