Pax4, also known as Paired box 4, is a key transcription factor. It has a conserved paired box domain and a homeodomain, and is essential in the embryonic development of pancreatic islets of Langerhans. It is crucial for cell-fate commitment of early endocrine progenitor cells towards the insulin-secreting β-cell lineage. Mutations in Pax4 are associated with diabetes pathogenesis in humans [1].

In animal models, knockout of Pax4 leads to the absence of β-cells, accompanied by a significant increase in glucagon-producing α cells, and typically results in lethality within days after birth [1]. In a human context, a coding variant (p.Arg192His) in PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. PAX4 knockdown in human beta cell models led to impaired insulin secretion, reduced total insulin content, and altered hormone gene expression [2].

In conclusion, Pax4 is vital for pancreatic β-cell development. Gene knockout models, both in animals and human cell models, have revealed its role in β-cell formation and function, and its association with diabetes. Understanding Pax4's function provides potential therapeutic targets for diabetes treatment, such as protecting and regenerating β-cells [1,2].