EVI2B (ecotropic viral integration site 2B) is a transmembrane glycoprotein (CD361) that functions as a critical regulator of hematopoietic differentiation and progenitor cell functionality. As a direct transcriptional target of C/EBPα, EVI2B is essential for granulocytic differentiation, with highest expression levels in mature granulocytes 1. EVI2B controls cell proliferation and apoptosis in hematopoietic progenitors; its downregulation impairs myeloid lineage development and compromises G-CSF-dependent myeloid colony formation 1. The gene is embedded within intron 27b of the NF1 gene and is significantly downregulated in acute myeloid leukemia samples with CEBPA defects 1. Beyond hematopoiesis, EVI2B exhibits broader disease relevance. It is involved in melanocyte and keratinocyte differentiation, with elevated expression in NF1-associated neurofibromas 2. Recent evidence identifies EVI2B as a pro-steatotic driver in metabolic dysfunction-associated fatty liver disease (MAFLD), with overexpression exacerbating lipid accumulation 3. Conversely, EVI2B is downregulated in lung adenocarcinoma, correlating with poor survival 4, and serves as a protective prognostic marker in osteosarcoma, correlating with macrophage infiltration 5. EVI2B also represents a potential drug resistance marker in multiple myeloma 6 and participates in immune dysregulation linking systemic lupus erythematosus and moyamoya disease 7.