Serine/threonine-protein kinase TAO1

TAO1 (TAOK1) is a serine/threonine-protein kinase that regulates stress-activated MAPK signaling, DNA damage responses, and cytoskeletal stability. It phosphorylates downstream effectors MAP2K3, MAP2K6, and MARK2, with the latter phosphorylation promoting tau detachment from microtubules (UniProt: Q7L7X3). The kinase also modulates apoptotic pathways through JNK cascade activation and plays essential roles in neuronal development and migration in the central nervous system.

TAO1 is implicated in developmental neurobiology, with mutations associated with developmental delay and intellectual impairment or behavioral abnormalities (DDIB; UniProt: Q7L7X3). Its function in tau regulation and stress response pathways suggests relevance to neuronal homeostasis.

In Alzheimer's disease, TAO1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.86 across analyzed subcellular fractions (Chaparral AD proteomics). This downregulation may reflect impaired stress response capacity or altered cytoskeletal dynamics in the AD brain pathology.