Three protein isoforms have been described for human GNE, where isoform 1 is ubiquitously expressed and is believed to be responsible for the basic supply of sialic acids. Isoforms 2 and 3 are generated by alternative splicing and show tissue specific expression patterns. Isoforms 2 and 3 have reduced epimerase activities but almost intact kinase activities and may fine-tune the production of sialic acids [9] . Wild type GNE forms homohexamer in solution [10] , and allosteric regulation of the epimerase and kinase activities of GNE is important for the normal function of the protein [10, 11] . Mutations in the epimerase domain lead to the rare congenital metabolism disorder sialurea, which results in the production of high levels of Neu5Ac due to loss of the allosteric feedback control of the UDP-GlcNAc 2-epimerase activity by CMP-Neu5Ac [12] . Late onset autosomal recessive inclusion body myopathy, which is also known as hereditary inclusion body myopathy (hereinafter referred to as HIBM), and allelic Nonaka myopathy are neuromuscular disorders that are caused by a number of different mutations within the gne gene. The mutations are located at either the epimerase domain or the kinase domain [13] and lead to hypoactivity of the enzyme [11] . Mutagenesis and enzymatic activity analysis revealed that the activities of the epimerase domain and the kinase domain are interrelated such that a single mutation in one domain could affect the activities of both domains [11] . Here, we solved the structure of the dimeric GNE kinase domain in the ligand-free state. The structure reveals the dimerization interface of the kinase domain and also suggests a possible hexameric assembly of the protein. Furthermore, the structure provides insights into the relationship between GNE mutations and GNE-related metabolism disorders.