4-phenylbutyrate promoted wildtype GABA A receptor trafficking, reduced Endoplasmic reticulum stress and mitigated seizures in Gabrg2 +/Q390X mice associated with Dravet syndrome.

receptor mutations through an unconventional antiseizure mechanism. Rather than directly modulating the affected mutant channel, PBA facilitates the folding and transportation of wildtype receptor subunits to the cell membrane and synapse. Combining these findings with our previous study, which demonstrated PBA's efficacy in restoring GABA transporter 1 (encoded by SLC6A1) function, we propose that PBA holds significant potential for a wide range of genetic epilepsies. Its ability to target shared molecular pathways involving mutant protein ER retention and impaired protein membrane trafficking suggests a broad application in treating such conditions.