Abstract: Tau protein is a main member of microtubule-associated proteins, hyperphosphorylation of tau is associated with many central nervous system diseases, such as Alzeimer's disease, epilepsy, frontal-temporal dementia, corticobasal degeneration, progressive supranuclear palsy, prion diseases and so on. Tauopathies are age-related neurodegenerative diseases that are characterized by the presence of aggregates of abnormally phosphorylated tau. Tauopathies can be classified into 6 isoforms according to the alternative splicing of MAPT. Exons 9, 10, 11, and 12 each encodes a microtubule binding motif. Isoforms that include exon 10 are commonly referred to as four-repeat or 4R tau isoforms while those that exclude exon 10 are referred to as threerepeat or 3R tau isoforms. 3R tau predominates in Pick's disease (PiD), whereas 4R tau predominates in corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Depending upon the specific mutation in MAPT, familial FTLD-tau have 3R, 4R or a combination of 3R and 4R tau. This article provides an overview of tau structure, functions, and its involvement in neurodegenerative diseases.