Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders

Tau, mainly expressed in neurons and less expressed in glial cells (astrocytes and oligodendrocytes) and peripheral tissues, is involved in the assembly and stabilization of microtubules, and other biological processes such as axonal transport, metal ion transport, etc. Dysfunction of tau, caused by mutations, hyperphosphorylation, aggregation, or reduced expression, is closely associated with tauopathies (e.g., Alzheimer disease) and psychiatric disorders. Tau-based biomarkers have emerged as predictive/diagnostic tools for these conditions. However, despite advancing to clinical trials, tau-targeted therapies have demonstrated limited efficacy in diseases. Therefore, this review aims to systematically summarize tau's physiological and pathological functions, the progress in tau-targeted therapies, and the development of tau as a disease biomarker, as well as to discuss critical gaps in understanding tau's pathophysiological roles and therapeutic translatability.