HOXA5 is a sequence-specific transcription factor that functions as a developmental regulator specifying anterior-posterior cellular identity 1. Beyond embryonic development, HOXA5 plays critical roles in hematopoietic stem cell specification and multiple disease contexts. It is a master transcription factor sufficient to convert hemogenic endothelium into functional hematopoietic stem and progenitor cells capable of multi-lineage engraftment 12. In adipose tissue, HOXA5 promotes anti-inflammatory M2 macrophage polarization and regulates adipocyte function and tissue remodeling, with DNA methylation-based downregulation of HOXA5 associated with hypertrophic obesity and type 2 diabetes risk 34. HOXA5 upregulation impairs airway epithelial differentiation; nylon microplastic fiber exposure upregulates HOXA5 and inhibits developing airway organoid formation, and HOXA5 inhibition restores this capacity 5. In cardiac pathology, HINT1 attenuates cardiac hypertrophy by suppressing HOXA5 expression via the MEK/ERK/YY1 pathway, implicating HOXA5 in TGF-β-mediated hypertrophic responses 6. HOXA5 serves as a fibroblast-specific transcriptional motif in intrahepatic cholangiocarcinoma, participating in cancer-associated fibroblast-tumor cell interactions 7. Prenatal maternal asthma exposure associates with altered HOXA5 DNA methylation in newborn blood, suggesting epigenetic mechanisms linking maternal asthma to offspring lung disease susceptibility 8.