NF-E2 belongs to the basic-leucine zipper family of dimeric transcription factors. It consists of a widely expressed 18 kDa subunit, related to chicken Maf proteins, and a tissue-restricted 45 kDa subunit, which contains a cnc domain. It is found almost exclusively in hematopoietic progenitors, and cells of the erythroid/mega/mast cell trilineage. NF-E2 is involved in regulation of globin gene transcription, acting through locus control regions (LCRs) upstream of the alpha and beta globin gene clusters. In addition, it is essential for normal platelet production. Targeted disruption of the gene encoding the 45 kDa subunit leads to severe thrombocytopenia but little if any defect in erythropoiesis, indicating that other molecules can substitute for p45 in red cell maturation in developing mice. However, retroviral integration within the p45 gene has been shown to disrupt erythroid differentiation in erythroleukemia cells; this suggests that p45 could, conceivably, be a target for pharmacologic interventions in patients with excess red cell production due to polycythemia vera.