Tau is a microtubule-associated phosphoprotein (MAP) localized in neuronal axons. It promotes tubulin polymerization and stabilizes microtubules. Tau proteins constitute a family of six isoforms ranging in size from 352 to 441 amino acids. The tau variants differ from each other in the presence or absence of either three or four repeat-regions near the carboxy-terminal and the presence or absence of one or two inserts near the amino-terminal. Tau is hyperphosphorylated by ERK, GSK-3, TPKII, and CDK5. Over thirty phosphorylation sites have been described, including Thr39, Ser46, Thr50, Thr69, Thr153, Thr175, Thr181, Ser198, Ser199, Ser202, Thr205, Ser208, Ser210, Thr212, Ser214, Thr217, Thr231, Ser235, Ser237, Ser241, Ser262, Ser285, Ser305, Ser324, Ser352, Ser356, Ser396, Ser400, Thr403, Ser404, Ser409, Ser412, Ser413, Ser416, and Ser422. Specifically, TPKII phosphorylates serines 202 and 404. GSK-3β transfection phosphorylates serines 199, 202, 235, 396, 404, and 413 and threonines 205 and 231. These sites are among the major abnormal phosphorylation sites of Tau. Phosphorylation on these sites reduces the ability of a given tau species to promote microtubule self-assembly. Hyperphosphorylated tau is the major protein found in the paired helical filaments (PHFs), which make up the pathological neurofibrillary tangles of Alzheimer’s disease (AD). These PHFs are also found in the lesions of other central nervous system disorders.