TANC2 is a postsynaptic scaffolding protein essential for brain development and synaptic function. It localizes to dendritic spines where it serves as an immobile structural component of the postsynaptic density, recruiting dense core vesicles and interacting with multiple synaptic proteins 1. Mechanistically, TANC2 directly inhibits mTORC1/2 signaling in developing neurons, a function distinct from other mTOR inhibitors and critical for normal neurodevelopment 2. Loss of TANC2 disrupts the balance between excitatory and inhibitory neurons, leading to excitatory/inhibitory imbalance 3. Pathogenic TANC2 variants cause a spectrum of neurodevelopmental disorders correlating with mutation severity. Null variants typically cause developmental and epileptic encephalopathy (DEE) with severe phenotypes, while missense variants present with milder manifestations ranging from isolated epilepsy to autism with intellectual disability 4. Common clinical features include autism spectrum disorder (70.6%), intellectual disability (94.1%), language delay (88.2%), epilepsy, and motor impairment 5. TANC2-disrupting mutations also associate with psychiatric dysfunction and behavioral problems in adults 1. Beyond the nervous system, TANC2 has pleiotropic functions affecting growth and hepatic metabolism through Hippo pathway interactions 6. These findings establish TANC2 as a critical regulator of both neural development and neuropsychiatric phenotypes.