TEAD2 (TEA domain transcription factor 2) is a key transcriptional regulator in the Hippo signaling pathway that plays critical roles in cancer progression and therapeutic resistance. TEAD2 functions as a DNA-binding transcription factor that requires interaction with coactivators like YAP and TAZ to regulate gene expression, as it lacks intrinsic transcriptional activation ability 1. The protein adopts an immunoglobulin-like beta-sandwich fold with a YAP-binding domain that forms extensive contacts with YAP through localized conformational changes 2. In hepatocellular carcinoma (HCC), TEAD2 drives tumor growth through a cholesterol-TAZ-TEAD2-ANLN/KIF23 pathway that promotes cell proliferation 3. TEAD2 also mediates sorafenib resistance in HCC by transcriptionally activating TAK1, making the TEAD2-TAK1 axis a potential therapeutic target 4. In pancreatic cancer, TEAD2 shapes basal-like differentiation and metastasis through a proangiogenic enhancer landscape and CD109-JAK/STAT signaling 5. Additionally, TEAD2 mRNA stability is regulated by METTL1-mediated m7G modification, which impacts mitochondrial function through ACADM repression in acute kidney injury 6. Pharmacological disruption of TEAD-YAP interactions represents a viable therapeutic strategy for YAP-driven oncogenic growth 7.