The formation of nucleotide hexosamines, primarily UDP-N-acetylglucosamine, constitutes the final step in the hexosamine biosynthetic pathway which provides substrates for the O-linked glycosylation of proteins. Glycoproteins that are either secreted from the cell or inserted into the plasma membrane undergo N-linked glycosylation. The O-linked glycosylation of nuclear and/or cytosolic proteins confers a signaling dimension to the hexosamine biosynthetic pathway.