TTBK2 (tau tubulin kinase 2) is a serine/threonine kinase with dual roles in ciliogenesis and neuronal pathology. Functionally, TTBK2 serves as a critical regulator of cilia initiation by localizing to the distal appendages of the mother centriole through interaction with CEP164 1. This interaction occurs via phase separation and facilitates TTBK2's primary function: promoting CCP110 removal and recruiting IFT proteins necessary for ciliary axoneme assembly 1. TTBK2 restrains the microtubule-depolymerizer KIF2A through phosphorylation, supporting cilia elongation and maintenance 2. Mechanistically, TTBK2 phosphorylates multiple substrates including tau, tubulin, CEP164, CEP97, and TDP-43 3. Notably, TTBK2 phosphorylates MPHOSPH9, promoting its degradation and facilitating CP110-CEP97 complex removal 3. Disease-wise, TTBK2 mutations cause spinocerebellar ataxia type 11 (SCA11), an autosomal dominant cerebellar ataxia 4. SCA11-associated truncations impair both ciliogenesis and TTBK2 kinase function against neuronal targets like tau and TDP-43, potentially driving neurodegeneration 4. Additionally, TTBK2 phosphorylates pathological TDP-43, relevant to amyotrophic lateral sclerosis and frontotemporal dementia 5. Clinically, TTBK2 represents a therapeutic target for both cerebellar ataxias and neurodegenerative proteinopathies 6.