MECP2 and atypical Rett syndrome: While trofinetide’s FDA approval for Rett syndrome demonstrates established CNS penetration and favorable safety profiles, the mechanistic disconnect between MECP2-related transcriptional dysregulation (Rett syndrome) and amyloid/tau proteinopathy (Alzheimer’s disease) necessitates systematic validation in transgenic AD mice, evaluating the effects on disease-relevant pathologies and cognitive outcomes.