The downregulation of REST may disrupt the homeostatic balance of astrocytes in DS.<h4>Methods</h4>This study aims to elucidate the role of REST in DS-astrocytes through comprehensive transcriptomic analysis and experimental validation.<h4>Results</h4>Transcriptomic analysis identified that REST-targeted differentially expressed genes (DEGs) in DS astrocytes are enriched in pathways associated with inflammatory response. The gene discussed is REST; the disease is Dravet syndrome.