A large number of patients are suffering from developmental disabilities, including Kaufman oculocerebrofacial syndrome (KOS). KOS is a severe autosomal recessive disorder characterized by general developmental delay with intellectual disability, hypocholesterolemia, and seizures. Ube3b, an E3 ligase gene, has been reported as the causative gene for KOS. Our previous report demonstrated a loss of murine Ube3b increases the number of dendritic spines at the age of three weeks, indicating that Ube3b is a negative regulator of synaptogenesis for the excitatory synapses in the early developmental stage. In this study, using brain-specific conditional Ube3b knockout (Ube3b bKO) mice, we investigated the further role of Ube3b in the young adult period. Mouse brain sections were prepared from 9-10 weeks old mice and immunostained with antibodies to Bassoon and Homer1, respective markers for presynapse and excitatory postsynapse. Images from hippocampal CA1 region were acquired with 3D Stimulated Emission Depletion (3D-STED) microscopy to estimate the excitatory synapse numbers. We found that the excitatory synapse density significantly decreased in Ube3b bKO as compared to the control. Together with our previous reports, our results indicate the novel role of Ube3b in the maintenance of synapse numbers in the young adult period.