Axonal outgrowth is a prerequisite for the development of the most complex organ, the brain. It depends partially on the attachment of sialic acid on glycans of (sialo)-glycoproteins expressed on the plasma membrane. In our study, we showed that nerve growth factor-induced neurite outgrowth of PC12-cells enhances the expression of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase (GNE), the key enzyme for the biosynthesis of sialic acid. Furthermore, we could show that overexpression of GNE induces neurite outgrowth in PC12 cells. The neurite-outgrowth promoting activity of overexpressed GNE, however, does not lead to an increased biosynthesis of sialic acid. These data suggest a novel role of GNE during neurite outgrowth, which is independent to its specific enzymatic activity.