IKZF2 (Helios) is a hematopoietic transcription factor that functions as a critical regulator of immune homeostasis and T cell differentiation. As a zinc finger DNA-binding protein, IKZF2 stabilizes the noninflammatory phenotype of regulatory T cells (Tregs) 1 by repressing IL2 transcription through epigenetic silencing and histone deacetylation [PMID:37316189, UniProt annotation]. IKZF2 is required for FOXP3 recruitment to the IL2 promoter in Tregs 2, and marks recent thymic emigrants alongside SOX4 and TOX expression 3. In disease contexts, IKZF2 dysregulation contributes to hematologic malignancies. Frequent IKZF2 alterations occur in adult T cell leukemia/lymphoma 4 and low-hypodiploid acute lymphoblastic leukemia (present in 53% of cases) 5. IKZF2 deletion in CAR T cells enhances anti-tumor efficacy against glioblastoma by promoting effector function and inhibiting T cell exhaustion 6. Selective IKZF2 degradation via NVP-DKY709 reduces Treg suppressive activity and rescues exhausted T cell function in cancer immunotherapy 1, while dual IKZF2/CK1α degradation blocks AML cell growth and induces myeloid differentiation 7. IKZF2 deficiency in Tregs correlates with autoimmune manifestations in DOCK11-deficient patients 2, highlighting its role in preventing immune dysregulation.