Abstract
Tau is a protein that is highly enriched in neurons and was originally defined by its ability to bind and stabilize microtubules. However, it is now becoming evident that the functions of tau extend beyond its ability to modulate microtubule dynamics. Tau plays a role in mediating axonal transport, synaptic structure and function, and neuronal signaling pathways. Although tau plays important physiological roles in neurons, its involvement in neurodegenerative diseases, and most prominently in the pathogenesis of Alzheimer disease (AD), has directed the majority of tau studies. However, a thorough knowledge of the physiological functions of tau and its post-translational modifications under normal conditions are necessary to provide the foundation for understanding its role in pathological settings. In this review, we will focus on human tau, summarizing tau structure and organization, as well as its posttranslational modifications associated with physiological processes. We will highlight possible mechanisms involved in mediating the turnover of tau and finally discuss newly elucidated tau functions in a physiological context.