Ikaros and Aiolos (IKZF1 and IKZF3)

Ikaros and Aiolos are zinc finger transcription factors belonging to the Ikaros family, which regulate the development, differentiation, and function of lymphoid lineages—including T cells, B cells, and natural killer (NK) cells[4][5][7]. Both proteins play critical roles in gene expression programs that shape hematopoietic and immune cell fate. Ikaros and Aiolos exert context-dependent transcriptional repression and activation by recruiting chromatin remodeling complexes, such as histone deacetylases, to target loci[3][4]. They are key regulators of apoptotic pathways, cytokine signaling, and lineage specification, and are essential for normal and neoplastic hematopoiesis[1][2][5]. Therapeutically, Ikaros and Aiolos are the primary targets of immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide, which promote the cereblon-dependent degradation of both proteins and are used in multiple myeloma, lymphoma, and certain leukemias. Loss or mutation of these proteins is linked to poor prognosis and resistance in some leukemias.

Other names

IKZF1Ikaros family zinc finger protein 1IKZF3Ikaros family zinc finger protein 3

Targeted protein degradation via cereblon (CRBN)-mediated ubiquitination and proteasomal degradation (IMiDs promote CRBN binding to Ikaros and Aiolos, leading to their destruction) - Modulation of immune cell function through changes in cytokine production and lymphocyte subset balance