PBX1 is a TALE-class homeodomain transcription factor that functions as a sequence-specific DNA-binding transcription regulator with context-dependent roles in development and disease 1. In pancreatic development, PBX1 participates in transcriptional activation complexes regulating tissue-specific genes. Beyond developmental functions, PBX1 has emerged as a critical regulator in multiple pathological processes. In hepatic stellate cells, PBX1 upregulation during activation promotes liver fibrosis by transcriptionally activating IL-7 receptor, which cooperates with TGF-β signaling to drive myofibroblast differentiation 2. In lupus nephritis, lactate-induced lactylation of PBX1 at Lys40 triggers its ubiquitin-mediated degradation, reducing P27 expression and causing aberrant mesangial cell proliferation 3. Conversely, PBX1 maintains regulatory T cell homeostasis and suppressive function; loss of PBX1 or expression of dominant-negative isoforms impairs Treg stability and promotes lupus-like autoimmunity 4. In gastric cancer, METTL3-mediated mRNA stabilization of PBX1 increases GCH1 expression and tetrahydrobiopterin production, promoting tumor progression 5. Additionally, PBX1 shows copy number gains in European intrahepatic cholangiocarcinoma and correlates with poor prognosis 6. In acute lung injury, engineered TAT-PBX1 fusion protein reduces inflammatory responses through AMPK-TFAM pathway activation 7. PBX1 genetic variants associate with lupus susceptibility and congenital urinary tract anomalies.