Tau protein is expressed abundantly in neurons and has a number of functions in the central nervous system. Tau binds to microtubules and leads to their assembly, stabilization, and maintenance. Tau also regulates motor-driven axonal transport. Phosphorylation of tau is a common post-translational modification that plays an important role in the solubility, localization, and function of tau. Conformational changes in tau have been linked to excessive phosphorylation of this protein, and decreased microtubule binding and stability. Hyperphosphorylated tau has a propensity to accumulate and form protein aggregates in neurons. These aggregates eventually form intracellular filamentous inclusions, known as neurofibrillary tangles (NFTs), that are detected biochemically and immunohistologically in neurodegenerative disorders termed Tauopathies. Hyperphosphorylated and aggregated tau interferes with normal neuronal function, such as microtubule dynamics, and ultimately leads to neurodegeneration.