We report that TBA improves BDNF-YFP trafficking and activity-dependent release in Mecp2 knockout hippocampal neurons to reach wildtype levels, suggesting that HDAC6 is a potential therapeutic target to restore BDNF-dependent neurological function in the absence of functional MeCP2, which provides a novel approach for therapeutic intervention in RTT. Here, HDAC6 is linked to Rett syndrome.