PBX4 (PBX homeobox 4) is a transcription factor belonging to the PBX family that functions as a transcriptional cofactor of HOX proteins, participating in various developmental and pathophysiological processes 1. As a DNA-binding transcription factor with RNA polymerase II-specific activity, PBX4 regulates gene expression in the nucleus and is involved in brain development, embryonic organ development, eye development, and neuron development based on its GO annotations. The gene shows significant clinical relevance in multiple disease contexts. In cancer, PBX4 is differentially expressed across 17 cancer types and is associated with pathological stage, tumor grade, and immune subtypes 1. Specifically in colorectal cancer, PBX4 upregulation is associated with increased proliferation, epithelial-mesenchymal transition marker expression, and worse overall survival 2. The protein also plays important roles in metabolic regulation, with genetic variants near PBX4 showing associations with serum lipid levels, including LDL cholesterol and triglycerides 34. Additionally, PBX4 has been identified as a pleiotropic gene linking nonalcoholic fatty liver disease and coronary artery disease 5, and variants are associated with plasma procalcitonin concentrations, suggesting involvement in calcium metabolism and immune function 6. In hematologic malignancies, low PBX4 expression is observed in acute lymphoblastic leukemia patients 7.