TCF3 (E2A) is a basic helix-loop-helix transcription factor that functions as a master regulator of lymphocyte development and differentiation. It facilitates DNA binding at E-box consensus sequences (5'-CAGGTG-3') and positively regulates transcriptional activity through heterodimerization and interaction with coactivators like EP300/CBP 1. TCF3 is essential for early B and T lymphocyte differentiation, with two functional wild-type copies required for tightly regulated gene dosage-dependent transcriptional programs 2. In Burkitt lymphoma, TCF3 functions as an oncogenic transcription factor in approximately 70% of sporadic cases, where mutations affecting TCF3 or its negative regulator ID3 foster TCF3 dependency 3. TCF3 activates pro-survival phosphatidylinositol-3-OH kinase signaling and maintains tonic B-cell receptor signaling essential for lymphoma cell survival 4. TCF3 also acts as a β-catenin-binding transcription factor in canonical Wnt signaling, transactivating oncogenic lncRNAs such as CCAT5 in gastric cancer 5. Clinically, monoallelic loss-of-function TCF3 mutations cause gene-dosage-dependent immunodeficiency with reduced B-cell populations and serum immunoglobulin levels 2. Biallelic TCF3 mutations produce severe primary immunodeficiency (agammaglobulinemia 8A/8B) 2. TCF3-PBX1 fusion-positive acute lymphoblastic leukemia shows poor prognosis but responds to CD19 CAR-T-cell therapy 6.