PTEN gene mutations, which cause neurodevelopmental disorders including autism and epilepsy, drive abnormal brain enlargement through the ARP2/3 protein complex acting downstream of hyperactive mTOR signaling pathways. The research identifies a specific molecular cascade where PTEN deficiency leads to mTORC1 and mTORC2 overactivation, subsequently triggering ARP2/3-mediated cellular changes that result in brain overgrowth pathology. This discovery fills a critical gap in understanding how PTEN mutations translate into the characteristic neurological symptoms observed in affected patients. The identification of ARP2/3 as a key mediator offers potential therapeutic leverage, as this protein complex regulates cytoskeletal dynamics essential for proper neural development. Unlike previous research focused primarily on mTOR itself, this work reveals how downstream effectors execute the pathological program. The findings suggest that targeting ARP2/3 or its regulatory mechanisms could provide more precise intervention strategies than broad mTOR inhibition, which often produces unwanted side effects. For families affected by PTEN-related disorders, this research represents meaningful progress toward understanding the biological basis of these conditions and potentially developing more targeted treatments that address the root cellular mechanisms rather than just managing symptoms.