NFE2 (nuclear factor, erythroid 2) is a transcription factor that forms heterodimers with small MAF proteins to regulate gene expression in hematopoietic cells 1. The NFE2-MAF complex binds to regulatory elements containing TCAT/C sequences in target gene promoters 1. While initially characterized as a regulator of globin gene expression, NFE2 knockout mice revealed that its primary function is controlling megakaryocyte biogenesis and platelet production, with only mild erythroid abnormalities observed 1. Beyond hematopoietic roles, recent evidence demonstrates that NFE2 functions in non-hematopoietic tissues including trophoblast and bone 1. Mechanistically, NFE2 activity is controlled through posttranslational modifications and operates within regulatory networks involving transcription factors such as GATA1 and RUNX1 1. Clinically, NFE2 dysregulation has been linked to hematological disorders including polycythemias 1. Emerging research reveals NFE2's role in pathological processes: it drives neutrophil polarization in pancreatic cancer liver metastasis through TGF-β-SMAD3 pathway activation, promoting neutrophil extracellular trap formation at invasive fronts 2. Additionally, NFE2L2 (an NFE2 family member) participates in retrograde mitochondrial-nuclear signaling affecting retinal pigment epithelial heterogeneity in age-related macular degeneration 3.