Tau tubulin kinase 2 (TTBK2)

Tau tubulin kinase 2 is a multifunctional serine/threonine protein kinase in the casein kinase 1 superfamily that phosphorylates tau and tubulin, among other substrates. It is structurally characterized by a CK1 kinase domain with a distinctive long C-terminal region involved in cellular localization and substrate recruitment[1][5][7]. TTBK2 localizes primarily to the basal body and centriole, where it plays an essential role in the initiation of ciliogenesis by promoting removal of CP110 and recruitment of proteins necessary for ciliary axoneme elongation[2][3]. It is widely expressed in multiple tissues, with high levels in the brain—especially in the cerebellum—and testis[7]. Mutations in TTBK2 are causative for autosomal dominant spinocerebellar ataxia type 11 (SCA11), a degenerative neurological disorder characterized by cerebellar dysfunction and neurodegeneration[1][3][6]. The kinase is also involved in cellular mechanisms related to cancer resistance and glucose transport, and its phosphorylation of tau protein is implicated in the early molecular alterations of Alzheimer's disease[4][7]. TTBK2 remains a promising target for therapeutic intervention in neurodegenerative and ciliopathy disorders.

Other names

TTBK2Tau-tubulin kinase 2KIAA0847SCA11TTBK

Kinase inhibition (drugs targeting TTBK2 generally act as ATP-competitive kinase inhibitors)