Rodin-B is an orally active, brain-penetrant, and selective inhibitor of the histone deacetylase (HDAC)-suppressor of transcription factor corepressor element-1 silencing transcription factor (CoREST) complex. It exhibits an IC50 value of 0.50 μM for the CoREST complex, 0.27 μM for HDAC1, and 0.28 μM for HDAC2. Rodin-B enhances the acetylation level of histone H3K9 and upregulates neuron-related gene expression, promoting increased dendritic spine density, colocalization of synaptic proteins (SV2A and PSD95), and improved hippocampal long-term potentiation (LTP), thereby exerting synaptic protection and repair effects. Rodin-B holds potential for research into neurodegenerative diseases related to synaptic dysfunction, particularly Alzheimer's disease.