FEZF2 (FEZ family zinc finger 2) is a transcription factor with critical roles in neurodevelopment and immune tolerance. In the nervous system, FEZF2 functions as a transcriptional regulator essential for cortical layer specification, particularly controlling the development of layer 5-6 pyramidal neurons and corticospinal motor neurons 1. The protein regulates neuronal subtype-specific gene expression patterns, with distinct L5-6_Fezf2 neuronal subtypes showing significant transcriptomic changes in epilepsy 1. FEZF2-positive neurons with unique morphologies, including fork cell-like neurons with characteristic dual apical dendrites, have been identified in the mouse insular cortex 2. Beyond neurodevelopment, FEZF2 plays a crucial role in immune tolerance by regulating tissue-specific antigen (TSA) expression in medullary thymic epithelial cells (mTECs), working alongside AIRE to control autoimmune disease development 34. FEZF2 deficiency is associated with autoimmune manifestations including type 1 diabetes and Sjögren's syndrome 3. Clinically, rare predicted deleterious variants in FEZF2 cause neurodevelopmental disorders characterized by intellectual disability, autism, and developmental delay 5. Additionally, FEZF2 functions as a tumor suppressor that is frequently methylated in nasopharyngeal carcinoma, where it normally represses oncogenes including EZH2 and MDM2 6.