Abstract: Tau is an important protein of the central nervous system formed by 352–441 amino acids and encoded by the MAPT (microtubule-associated protein tau) gene on chromosome 17 which generates 6 isoforms. Tau is located in axons, dendrites, nucleus, cell membrane, and synapses of neurons. The protein is also expressed to a lesser extent in astrocytes and oligodendrocytes, although its role in these cells has been little investigated. The protein is also present in the interstitial fluid and can cross into the cerebrospinal fluid (CSF) and reach the systemic circulation. The main function of tau is promoting the assembly and stabilization of microtubules in neuronal axons. Tau plays also a role in a range of other biological processes including myelination, neurogenesis, motor function, learning, and memory (Kent et al., 2020). The binding of tau to microtubules is regulated by its phosphorylation/dephosphorylation equilibrium. In physiological conditions, tau is unfolded and phosphorylated, while the pathological form is characterized by an excess of hyperphosphorylation leading to disengagement from the microtubules, and conformational changes that lead to the formation of paired helical and straight filaments of abnormally phosphorylated tau and subsequently to tau aggregates. These aggregates can cause degeneration of neurons and glial cells that ultimately lead to various clinical cognitive, behavioral, and motor manifestations, which are classified into different types of neurodegenerative disorders called ‘tauopathies’. Tauopathies are classified into primary and secondary tauopathies. In primary tauopathies, the abnormal tau accounts for the primary underlying neurodegenerative process. Primary tauopathies include progressive supranuclear palsy (PSP), corticobasal degeneration, corticobasal syndrome tauopathy, Pick’s disease, frontotemporal dementia, frontotemporal lobar degeneration, primary progressive aphasia, MAPT mutation, argyrophilic grain disease, and primary age-related tauopathy. In secondary tauopathies, tau neuronal inclusions occur in association with the extracellular deposition of a second aggregated protein. Secondary tauopathies include Alzheimer’s disease (AD) and Down syndrome (in which amyloid-beta [Aβ] accumulates), Lewy body dementia (in which α-synuclein accumulates), and chronic traumatic encephalopathy (in which TAR DNA-binding protein 43) accumulates.