SOX4 is a transcriptional activator that binds the T-cell enhancer motif 5'-AACAAAG-3' with high affinity 1 and plays multifaceted roles in both normal physiology and disease. As a sequence-specific DNA-binding transcription factor, SOX4 regulates gene expression programs critical for immune cell maturation, myoblast differentiation, and tissue homeostasis. In cancer immunity, SOX4 functions as a key regulator of T cell dysfunction and immune evasion. SOX4 downregulation improves CAR T cell efficacy in solid tumors by preventing exhaustion 2. In triple-negative breast cancer, integrin αvβ6-TGFβ signaling upregulates SOX4, which suppresses immune pathways and promotes resistance to cytotoxic T cells 3. In nasopharyngeal carcinoma, SOX4 governs zinc metabolism through ZIP14, creating a zinc-deficient microenvironment that impairs CD8+ T cell function 4. Conversely, in colorectal cancer, METTL14-mediated m6A modification of SOX4 mRNA promotes SOX4 degradation, reducing metastasis 5. Beyond cancer, SOX4 regulates endothelial-to-mesenchymal transition in atherosclerosis 6, mediates ferroptosis in kidney injury through EZH2-dependent mechanisms 7, and restrains acinar cell dedifferentiation in pancreatic injury 8. These findings establish SOX4 as a context-dependent regulator with therapeutic potential across multiple disease contexts.