ADNP is a transcriptional regulator and chr20-associated protein with critical roles in neurodevelopment. As a homeodomain-containing protein, ADNP functions as an RNA polymerase II transcription factor that regulates gene expression through chr20 binding 1. ADNP positively modulates Wnt-β-catenin signaling by stabilizing CTNNB1 through phosphorylation regulation and is required for neural induction and neuronal differentiation 1. Mechanistically, ADNP resolves R-loops—three-stranded nucleic acid structures that accumulate during neurological dysfunction—through its homeodomain, suppressing R-loop accumulation at genomic targets to maintain normal neuronal function 2. Loss-of-function mutations in ADNP are among the most frequent causes of autism and intellectual disability 3. ADNP mutations cause Helsmoortel-van der Aa syndrome, characterized by mild-to-severe intellectual disability, autism spectrum disorder, developmental delay, distinctive facial features, and common comorbidities including epilepsy, hypotonia, and cardiac defects 3. As a highly penetrant autism risk gene, individuals with ADNP loss-of-function variants show greater cognitive impairment (88%) compared to those with moderate-risk variants 4. ADNP mutations are implicated in approximately 0.3-1% of autism cases 5. The therapeutic peptide CP201 (NAP), derived from ADNP's microtubule-interacting domain, shows promise in preclinical models and may offer clinical benefits 6.