The vast majority of the human genome consists of noncoding elements, including introns, intergenic regions, and various types of noncoding RNAs (ncRNAs). As such, protein-coding genes represent only 1.5% of the transcriptome while the remaining 98,5% are ncRNAs. Long non-coding RNAs (lncRNAs) form the largest class of ncRNAs and are characterized by a length of more than 200 nucleotides. The role of lncRNAs in the central nervous system (CNS) is still not well understood. In this project we identified a novel lncRNA that we named CNS-LNC due to its specific expression pattern in the adult brain. We show that within the brain CNS-LNC is exclusively expressed in non-neuronal cell types in both human and mouse, with a particularly high expression in astrocytes. Here, CNS-LNC is localized to the nucleus suggesting a role in gene-expression control. Our functional analysis indicates that CNS-LNC expression is downregulated in reactive astrocytes. Knockdown (KD) of CNS-LNC in pAst leads to upregulation of virus response-related genes and downregulation of cilium organization and synapse-related genes. Furthermore, astrocyte condition medium from CNS-LNC KD cells affected neuronal activity when administer to neurons. In summary, our results suggest CNS-LNC as a novel regulator of astrocyte-mediated neuronal support function.