ARX is an X-linked transcription factor essential for neurodevelopment that binds the sequence motif 5'-TAATTA-3' in regulatory elements 12. It positively modulates transcription of target genes including histone demethylase KDM5C, functioning synergistically with PHF8 2. ARX operates as a bifunctional regulator, capable of both activating and repressing RNA polymerase II-dependent transcription 3. During brain development, ARX is critical for neuronal proliferation, interneuronal migration, and differentiation in the embryonic forebrain 4. ARX mutations rank among the most common causes of X-linked intellectual disability, found in approximately 9.5% of X-linked families and 1 in 12,000 male births, second only to Fragile X syndrome 56. Truncating mutations typically cause severe cortical malformations including X-linked lissencephaly with abnormal genitalia, characterized by lissencephaly, corpus callosum agenesis, and intractable seizures 7. In contrast, insertion and missense mutations produce epilepsy and intellectual disability without cortical dysplasia 7. ARX mutations account for up to 5% of infantile spasms cases and are associated with developmental and epileptic encephalopathy, autism spectrum disorder, and Partington syndrome 46. Female carriers with de novo variants show variable penetrance, with 41% manifesting severe phenotypes including intellectual disability 8.