IKZF1 (Ikaros family zinc finger 1) is a lymphoid transcription factor that serves as a master regulator of hematopoietic cell differentiation, particularly in B and T cell development 1. The protein functions as a sequence-specific DNA-binding transcription factor that binds gamma-satellite DNA and regulates gene expression through both HDAC-dependent and HDAC-independent mechanisms, targeting chr7-remodeling complexes NuRD and BAF to specific genomic loci 2. In regulatory T cells, IKZF1 associates with Foxp3 to repress gene expression and maintain immune tolerance; disruption of this interaction increases interferon-γ production and causes systemic autoimmunity 3. Clinically, IKZF1 deletions are strongly associated with poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (ALL), particularly when co-occurring with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 (IKZF1plus phenotype), with 5-year event-free survival of only 53% 45. IKZF1 is therapeutically targetable through cereblon-dependent degradation: lenalidomide and pomalidomide bind cereblon to selectively degrade IKZF1 and IKZF3, with this mechanism contributing to efficacy in multiple myeloma and myelodysplastic syndromes 678. Function is isoform-specific and can be modulated by dominant-negative inactive isoforms.