TCF20 is a transcriptional coactivator that regulates gene expression through multiple mechanisms relevant to neurodevelopment and metabolic homeostasis. As a nuclear chr22-binding protein, TCF20 stimulates transcriptional activators including JUN, SP1, PAX6, and ETS1, and controls stromelysin expression via MMP3 regulation 1. TCF20 functions as a component of the MeCP2-interacting TCF20/PHF14 chr22 complex, which orchestrates epigenetic and transcriptional regulation critical for brain development 2. Pathogenic TCF20 variants cause TCF20-associated neurodevelopmental disorders (TAND), characterized by developmental delay, intellectual disability, hypotonia, dysmorphic features, autism spectrum disorder, and movement disorders 1. Loss-of-function variants (frameshift, nonsense, and splice-site mutations) are the predominant pathogenic mechanism, with both de novo and inherited inheritance patterns documented; germline mosaicism represents an under-detected inheritance mode 3. Beyond neurodevelopment, TCF20 deficiency increases liver fibrogenesis susceptibility and alters mitochondrial oxidative phosphorylation, with metabolic alterations including elevated plasma succinate detected in affected patients 4. TCF20 duplications also cause neurodevelopmental disorder with mirror phenotypic traits 5. These findings establish TCF20 as a dosage-sensitive gene critical for proper neural development and metabolic function.