TLX1 (T cell leukemia homeobox 1) is a transcription factor that plays critical roles in both normal development and leukemogenesis. In normal development, TLX1 controls spleen genesis and is involved in placental trophoblast differentiation, where decreased expression during late gestation promotes proper placental function 1. As a DNA-binding transcription factor, TLX1 binds specific DNA sequences and regulates gene expression through cooperative enhancer activation 2. In T-cell acute lymphoblastic leukemia (T-ALL), TLX1 aberrant expression is associated with cortical T-ALL phenotype and represents a major oncogenic driver 3. TLX1 cooperates with STAT5 to co-bind poised enhancer regions and activate proto-oncogenes including MYC and BCL2, promoting leukemia development 2. The gene is frequently activated by chr10 translocations involving T-cell receptor loci at the 10q24 breakpoint cluster region 4. Transcriptomic analysis reveals TLX1-high expression defines specific T-ALL subtypes corresponding to cortical/postcortical T-cell development stages 5. Clinically, TLX1 expression correlates with specific mutation patterns including PTPN2 mutations in T-ALL 6, and genetic polymorphisms in TLX1 are associated with childhood ALL risk 7. Beyond hematologic malignancies, high TLX1 expression correlates with poor prognosis in lung adenocarcinoma 8.