TheLINC00473(Lnc473) gene has previously been shown to be associated with cancer and psychiatric disorders. Its expression is elevated in several types of tumors and decreased in the brains of patients diagnosed with schizophrenia or major depression. In neurons,Lnc473transcription is strongly responsive to synaptic activity, suggesting a role in adaptive, plasticity-related mechanisms. However, the function ofLnc473is largely unknown. Here, using a recombinant adeno-associated viral vector, we introduced a primate-specific humanLnc473RNA into mouse primary neurons. We show that this resulted in a transcriptomic shift comprising downregulation of epilepsy-associated genes and a rise in cAMP response element-binding protein (CREB) activity, which was driven by augmented CREB-regulated transcription coactivator 1 nuclear localization. Moreover, we demonstrate that ectopicLnc473expression increased neuronal excitability as well as network excitability. These findings suggest that primates may possess a lineage-specific activity-dependent modulator of CREB-regulated neuronal excitability.