The first two steps of the biosynthesis of Neu5Ac from UDP-GlcNAc are catalyzed by the bi-functional enzyme UDP-GlcNAc 2-epimerase/N-acetylmannosamine kinase (GNE). GNE contains an N-terminal epimerase domain and a C-terminal kinase domain [7] . The epimerase domain converts UDP-GlcNAc to Nacetylmannosamine (ManNAc), which is then phosphorylated at the 6 position by the kinase domain. GNE is feedback-inhibited by the activated form of Neu5Ac, i.e., cytidine-monophosphate Nacetylneuraminic acid (CMP-Neu5Ac). The kinase domain belongs to the ROK (Repressor, ORF, Kinase) family. The ROK family consists of a set of bacterial proteins that include repressors for sugar catabolic operons, and sugar kinases [8] . Gne is the only known gene in the entire human genome that encodes a ROK domain-containing protein.