HOXB8 is a homeobox transcription factor that plays critical roles in hematopoietic cell development and neurological function. In hematopoiesis, HOXB8 marks definitive hematopoietic lineages, including erythromyeloid progenitors, hematopoietic stem cells, and their progeny, particularly monocytes 1. The gene positively regulates granulocyte progenitor development, with HOXB8 expression peaking during early differentiation stages 2. A specialized subset of microglia expressing HOXB8 functions as critical regulators of behavior, acting as 'brakes' to reduce anxiety and pathological grooming behaviors 3. These HOXB8 microglia work in opposition to canonical non-HOXB8 microglia in a binary system controlling emotional and compulsive behaviors 4. Optogenetic stimulation of HOXB8 microglia in specific brain regions induces distinct behavioral responses: grooming in the dorsomedial striatum and medial prefrontal cortex, anxiety in the amygdala, and mixed responses in the hippocampus 4. In cancer contexts, HOXB8 is overexpressed in colorectal cancer and negatively regulated by miR-196, with this interaction affecting chemotherapy sensitivity 5. The gene's dysfunction leads to chr17 anxiety and obsessive-compulsive behaviors, highlighting its importance in neuropsychiatric regulation.