PDX1 is a homeodomain-containing transcription factor that serves as a master regulator of pancreatic development and β-cell function 1. Functionally, PDX1 activates transcription of critical genes including insulin, somatostatin, glucokinase, and glucose transporter type 2 (GLUT2), with particular importance in glucose-dependent insulin gene regulation 1. During development, PDX1 specifies the early pancreatic epithelium and duodenal patterning, acting downstream of RFX6 in intestinal development 2. In mature β-cells, PDX1 maintains the hormone-producing phenotype required for glucose homeostasis 1. Mechanistically, PDX1 functions as a sequence-specific DNA-binding transcription factor recognizing the motif 5'-[CT]TAAT[TG]-3' 1. Its transcriptional activity is enhanced by TAZ, a Hippo pathway co-activator that physically interacts with PDX1's homeodomain, promoting insulin production even under low-glucose conditions 3. Additionally, m6A methylation of PDX1-pathway transcripts regulates β-cell biology, with decreased m6A levels impairing PDX1 protein levels and insulin secretion 4. Clinically, PDX1 mutations cause monogenic diabetes (MODY4) and pancreatic agenesis 1. In cancer, PDX1 exhibits context-dependent roles: functioning as a tumor suppressor in gastric cancer while promoting tumorigenesis in pancreatic ductal adenocarcinoma 5. PDX1-targeted therapies show promise for PDAC treatment 6.