Tau-protein kinase I (TPK I)

Tau-protein kinase I is an outdated, umbrella term that has referred to multiple serine/threonine kinases capable of phosphorylating tau protein, most prominently in neural tissue. The phosphorylation of tau is central in the pathology of Alzheimer’s disease and other tauopathies, leading to the formation of neurofibrillary tangles. Over time, many kinases have been described as "tau kinases"—including glycogen synthase kinase-3 beta (GSK-3β), cyclin-dependent kinase 5 (CDK5), tau-tubulin kinase 1 (TTBK1), and TANK-binding kinase 1 (TBK1)—each with established roles in tau modification and neurodegeneration. Modern research refers to these kinases by their specific names rather than the nonspecific "Tau protein kinase I." Therefore, "Tau protein kinase I" should not be considered a single canonical drug target, but rather an outdated term for a set of tau-phosphorylating enzymes critical in tau biology and neurodegenerative disease.

Other names

Tau kinase[tau-protein] kinasetau-tubulin kinaseTPKTPK ITPK IIprotein tau kinaseGSK3 (Glycogen synthase kinase 3)CDK5/p23STK31TTKATP:tau-protein O-phosphotransferasebrain protein kinase PK40erk

Inhibition of tau kinase activity reduces hyperphosphorylation of tau, limiting its aggregation and neuronal toxicity. This is the principle behind GSK-3β and CDK5 inhibitors in tauopathies. TBK1 inhibitors block phosphorylation of tau at specific residues, reducing neurotoxicity in disease models.