Rodin-A is an orally active, brain-penetrant, and selective inhibitor of the histone deacetylase (HDAC) CoREST complex, exhibiting an IC50 value of 1.80 μM for the CoREST complex, 0.15 μM for HDAC1, and 0.43 μM for HDAC2. It enhances acetylation of histone H3K9 and upregulates neuronal gene expression, leading to increased dendritic spine density, co-localization of synaptic proteins (SV2A and PSD95), and improved hippocampal long-term potentiation (LTP), thus providing synaptic protection and repair. Rodin-A is a promising compound for the study of neurodegenerative diseases associated with synaptic dysfunction, particularly Alzheimer's disease.