CEBPD (CCAAT enhancer binding protein delta) is a transcription factor that recognizes CCAAT homology sequences common to many promoters and enhanced core homology sequences in enhancers. It functions as a key regulator of genes involved in immune and inflammatory responses, acting as a transcriptional activator that enhances IL6 transcription independently and synergistically with CEBPB 1. The protein is expressed at low or undetectable levels in normal tissues but is induced by lipopolysaccharide and inflammatory cytokines 1. In disease contexts, CEBPD exhibits significant pathogenic roles despite being relatively unconstrained at the population level. In Down syndrome-associated acute lymphoblastic leukemia, abnormal CEBPD activation occurs in 10.5% of cases through chr8 rearrangements and enhancer hijacking, where CEBPD overexpression promotes differentiation of hematopoietic progenitors into pro-B cells 2. In glioblastoma, CEBPD acts as a master transcriptional regulator of hypoxia-regulated proteins, driving invasion through EGFR/PI3K pathway activation via fibronectin-mediated mechanisms, with high CEBPD levels predicting poor prognosis 3. Recent evidence also suggests CEBPD serves as a key transcription factor in IL-21-engineered NK cells, where it regulates enhanced anti-tumor cytotoxicity and metabolic fitness against glioblastoma 4. These findings identify CEBPD as a potential therapeutic target in hematologic and solid malignancies, though translational approaches remain exploratory.