Tau-tubulin kinase 1 (TTBK1)

Tau-tubulin kinase 1 (TTBK1) is a serine/threonine/tyrosine protein kinase specifically expressed in the central nervous system and is a principal enzyme phosphorylating tau at AD-relevant sites (notably Ser422), contributing to tau hyperphosphorylation, aggregation, and neuronal dysfunction typical of Alzheimer’s disease and other tauopathies. As part of the casein kinase superfamily and closely related to TTBK2, TTBK1 regulates both tau protein and tubulin, and its overexpression aggravates neuroinflammatory and neurodegenerative processes. Its CNS-restricted expression and implication in tauopathy make it a novel and attractive therapeutic target, though challenges remain in achieving selectivity and avoiding off-target consequences.

Other names

Brain-derived tau kinaseBDTKKIAA1855Tau-tubulin kinase 1brain-derived tau kinase

Inhibition of kinase activity to reduce tau phosphorylation and aggregation; Interference with ATP binding at the active site