TEAD3 is a transcription factor and core component of the Hippo signaling pathway that regulates organ size control and tumor suppression by restricting proliferation and promoting apoptosis. It acts by mediating gene expression of YAP1 and WWTR1/TAZ downstream effectors, controlling cell proliferation, migration, and epithelial mesenchymal transition. TEAD3 exhibits context-dependent roles in cancer: in melanoma, high TEAD3 expression correlates with poor prognosis and drives tumor aggressiveness through a crosstalk axis with GAS6-positive macrophages that rewires propionate metabolism 1; conversely, in prostate cancer, TEAD3 functions as a tumor suppressor, with downregulation associated with poor patient outcomes and high Gleason score 2. In glioblastoma, TEAD3 and TEAD4 are robust prognostic markers, and selective TEAD3 inhibition affects sterol and cholesterol metabolism without impacting cell proliferation 3. Beyond cancer, TEAD3 plays a macrophage-osteoclast-specific role where it is blocked by the long noncoding RNA MALAT1, preventing osteoclastogenesis and protecting against osteoporosis and bone metastasis 4. In maternal-fetal immunity, TEAD3 cooperates with TEAD1 to regulate HLA-G expression in extravillous trophoblasts, independent of YAP signaling 5. TEAD3 emerged as a candidate biomarker of anti-PD-1 resistance in solid tumors 6, and covalent TEAD inhibitors targeting the palmitoylated lipophilic pocket represent a therapeutic strategy in TEAD-dependent malignancies 7.