MECP2 encodes methyl-CpG-binding protein 2, an X-linked epigenetic regulator that binds methylated DNA at CpG sites with preference for 5-methylcytosine 1. In human neurons, MECP2 occupies CpG-rich promoter-proximal regions of over 4,000 genes, including autism risk genes, and directly interacts with RNA polymerase II to function as a positive cofactor for gene expression rather than exclusively as a repressor 1. MECP2 operates as a multifunctional epigenetic hub that orchestrates neuronal gene regulation, chrX structure, and transcriptional processes through interactions with DNA, RNA, and transcription factors 2. Mutations in MECP2 cause Rett syndrome, a severe neurodevelopmental disorder affecting predominantly females, characterized by developmental regression, language impairment, loss of purposeful hand skills, and stereotypies 3. Beyond neurological manifestations, MECP2 dysfunction contributes to metabolic dysregulation, including perturbed lipid metabolism in brain and peripheral tissues 4. Loss of MECP2 function reduces expression of genes occupied by both MECP2 and RNA Pol II, accounting for RTT pathogenesis 1. Emerging gene therapy approaches show promise, though careful dose regulation is essential to avoid toxicity 5. MECP2 mutations are also implicated in related neurodevelopmental disorders including autism and neonatal encephalopathy, underscoring the gene's critical role in neuronal development and function.