TEAD3 is a transcription factor belonging to the TEA domain family that plays context-dependent roles in gene regulation and disease pathogenesis. As a component of the Hippo signaling pathway, TEAD3 mediates transcriptional responses downstream of YAP/TAZ, regulating cell proliferation, migration, and epithelial-mesenchymal transition 1. TEAD3 functions through DNA binding to regulatory elements and acts independently of YAP/TAZ in some contexts; for instance, in glioblastomas, TEAD3 specifically controls sterol and cholesterol metabolism without requiring YAP/TAZ interaction 2. In osteoclastogenesis, TEAD3 function is uniquely inhibited by the long noncoding RNA MALAT1, which blocks TEAD3-mediated activation of Nfatc1, thereby suppressing osteoclast differentiation and protecting against osteoporosis and bone metastasis 3. TEAD3 also functions in maternal-fetal immune tolerance by promoting HLA-G expression in extravillous trophoblasts through a YAP/TAZ-independent mechanism 4. Disease relevance varies by tissue context: in prostate cancer, TEAD3 acts as a tumor suppressor by inhibiting ADRBK2 expression 5, whereas in melanoma, TEAD3 drives progression through interaction with GAS6+ macrophages and propionate metabolism dysregulation 1. High TEAD3 expression correlates with anti-PD-1 immunotherapy resistance across multiple solid tumors 6, suggesting therapeutic targeting potential through selective TEAD inhibitors 7.