ZBTB18 is a zinc finger transcriptional repressor essential for neurodevelopment and metabolic homeostasis. In the nervous system, ZBTB18 directly represses ID2 and ID3 to promote skeletal myogenesis and regulates progenitor cell division and postmitotic cortical neuron survival 1. ZBTB18 is required for neuronal differentiation, as its loss causes cytoskeletal defects, stunted neurites, and impaired MAP2+ neuron production 1. The protein binds consensus E-box sequences and recruits chr1 remodeling complexes to regulate RNA polymerase II-dependent transcription [UniProt]. Beyond neurodevelopment, hepatic ZBTB18 alleviates non-alcoholic fatty liver disease by transcriptionally activating Farnesoid X Receptor (FXR), promoting fatty acid oxidation and suppressing NLRP3 inflammasome activity 2. In glioblastoma, ZBTB18 exhibits tumor-suppressive function by repressing cytokine production, reducing immune cell recruitment, and altering immune cell polarization 3. Pathogenic de novo variants in ZBTB18 cause autosomal dominant intellectual developmental disorder 22 (IDHD22), characterized by global developmental delay, motor deficits, and variable cognitive impairment 45. ZBTB18 emerges as a critical regulator across multiple biological systems, with disease relevance spanning neurodevelopmental disorders and metabolic disease 67.