NEUROG3 is a basic helix-loop-helix transcription factor serving as a master regulator of enteroendocrine and pancreatic endocrine cell differentiation. Functionally, NEUROG3 is both necessary and sufficient for human enteroendocrine cell development in vitro 1 and drives pancreatic endocrine progenitor specification 2. Mechanistically, NEUROG3 operates as a transcriptional activator with genome-wide occupancy at 863 binding sites across 1,263 genes, including direct regulation of key endocrine transcription factors (NEUROD1, PAX4, NKX2-2) and genes controlling insulin secretion (GCK, ABCC8, PCSK1) 2. NEUROG3 expression is induced transiently during endocrine differentiation protocols in pluripotent stem cells and can be activated by metabolic cues such as fasting mimicry 3. Clinically, NEUROG3 mutations cause enteric anendocrinosis and congenital diarrhea with diabetes mellitus and combined pituitary hormone deficiency 4. NEUROG3 has therapeutic potential in regenerative medicine—transient NEUROG3 expression enables directed differentiation into enteroendocrine cells from pluripotent stem cells 5, while combined expression with other transcription factors (Pdx1, MafA, Pax4, Nkx2-2) reprograms human fibroblasts into functional insulin-producing cells 6, offering novel approaches for diabetes treatment.