HOXB6 is a sequence-specific DNA-binding transcription factor that functions as a developmental regulator of anterior-posterior axis specification. During normal development, HOXB6 exhibits dynamic subcellular localization, with cytoplasmic expression in fetal epidermis and predominantly nuclear localization in differentiated adult tissues 1. HOXB6 plays a critical role in regulating myeloid differentiation, with transient expression during normal granulocytopoiesis and monocytopoiesis; enforced expression inhibits granulocytic and monocytic maturation 2. In disease contexts, HOXB6 emerges as a significant pathogenic factor. HOXB6 is frequently upregulated in acute myeloid leukemia cases lacking major translocations, suggesting roles in leukemogenesis 2. In colorectal cancer, HOXB6 expression is deregulated and serves as a direct target of miR-196B 3, 4. In pancreatic ductal adenocarcinoma, HOXB6 promotes tumorigenesis and suppresses anti-tumor immunity; HOXB6 loss inhibits proliferation, induces apoptosis, and enhances chemotherapy sensitivity while impairing immune evasion mechanisms 5. HOXB6 also drives treatment resistance in castration-resistant prostate cancer through promoting lineage plasticity 6. Additionally, HOXB6 serves as a diagnostic biomarker for endometriosis, where it participates in immune-inflammatory pathways and is potentially druggable by existing therapeutics 7. In rheumatoid arthritis, HOXB6 functions as a specific transcription factor in synovial macrophage subsets 8.