IKZF3 (IKAROS family zinc finger 3) encodes a transcription factor that plays essential roles in B-cell biology and immune regulation. The protein serves as a critical dependency factor in multiple myeloma cells, where its selective degradation by lenalidomide through the CRBN-CRL4 ubiquitin ligase represents a key therapeutic mechanism 1 2. IKZF3 functions in conjunction with IKZF1 as targets for immunomodulatory drugs, with their degradation being both necessary and sufficient for lenalidomide's therapeutic effects 2. In regulatory T cells, IKZF3 associates with Foxp3 and IKZF1 to form a complex that competes with co-activators like p300 for chr17 binding, thereby mediating gene repression and maintaining immune homeostasis 3. The protein is recurrently mutated in hematologic malignancies, including chr17 lymphocytic leukemia and hypodiploid acute lymphoblastic leukemia 4 5. Additionally, IKZF3 serves as a target for novel therapeutic approaches, including dual BTK/IKZF1/3 degraders like NX-2127, which demonstrate clinical efficacy in B-cell malignancies 6. These findings establish IKZF3 as a crucial transcriptional regulator whose modulation represents an important therapeutic strategy in hematologic cancers.