A landmark invited review published in Genomic Psychiatry provides a comprehensive synthesis to date of tau protein's complex roles in both health and disease. Dr. Peng Lei of Sichuan University and colleagues examine how tau, once considered merely a structural protein, participates in iron metabolism, synaptic plasticity, and insulin signaling while also driving pathology in Alzheimer disease, progressive supranuclear palsy, and, surprisingly, psychiatric conditions including schizophrenia and delirium. The synthesis spans over 300 referenced studies across more than four decades of research, revealing critical gaps in understanding tau's transition from physiological guardian to pathological driver. The review authors propose that tau dysfunction represents a convergence point for multiple neurodegenerative and psychiatric mechanisms, offering new frameworks for biomarker development and therapeutic intervention.