Ikaros family zinc finger protein 2 and Ikaros family zinc finger protein 4 (IKZF2/IKZF4)

IKZF2 (Helios) and IKZF4 (Eos) are members of the Ikaros family of zinc-finger transcription factors that play essential roles in the hematopoietic system, particularly in the regulation of T-cell identity and function [1, 3]. They are primarily expressed in regulatory T cells (Tregs), where they act as transcriptional repressors to maintain Treg stability and suppressive activity by inhibiting the production of effector cytokines such as interleukin-2 (IL-2) [6, 11, 12]. In the tumor microenvironment, these factors contribute to immune evasion by preserving the immunosuppressive state of Tregs, making them attractive targets for cancer immunotherapy [9, 14]. Therapeutic intervention typically involves molecular glue degraders, such as DKY709 and BMS-986449, which facilitate the recruitment of the CRL4-CRBN E3 ubiquitin ligase to induce the proteasomal degradation of IKZF2 and IKZF4 [1, 11]. This degradation leads to the reprogramming of Tregs into effector-like T cells, thereby enhancing anti-tumor immune responses [6, 9]. Beyond oncology, genetic variants in IKZF2 are associated with ICHAD syndrome, a condition characterized by immunodysregulation and sensorineural hearing loss, reflecting the protein's role in developmental processes [12, 13].

Other names

HeliosEosZinc finger protein HeliosZinc finger protein EosZNFN1A2ZNFN1A4Ikaros family zinc finger protein 2Ikaros family zinc finger protein 4

Targeted protein degradation via recruitment of the CRL4-CRBN E3 ubiquitin ligase complex