PREB (prolactin regulatory element binding) is a WD-motif transcription factor primarily identified for regulating pituitary gene transcription through binding to the prolactin gene promoter 1. The protein consists of 417 amino acids and exhibits structural features characteristic of WD-repeat protein families 12. Beyond its canonical role in prolactin regulation, PREB functions as a negative regulator of hepatic gluconeogenesis by directly binding prolactin core-binding elements (PCBE) in promoters of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase-1, thereby suppressing their expression 3. PREB is expressed ubiquitously across human tissues with variable levels, showing particularly robust expression during embryonic development in the anterior pituitary, peripheral nervous system, developing liver, and craniofacial skeleton 2. Clinically, PREB is relevant to trisomy 2p syndrome; the gene maps to chromosome 2, a region associated with this condition characterized by facial abnormalities, skeletal defects, growth retardation, and developmental abnormalities 1. The abnormal dosage of PREB in partial trisomy 2p likely contributes to these developmental phenotypes, suggesting PREB plays critical roles in human development beyond prolactin regulation. Recent evidence demonstrates PREB regulates glucose homeostasis, positioning it as a potential therapeutic target for metabolic syndrome and type-2 diabetes 3.