Tubulin-specific chaperone D

Tubulin-specific chaperone D (TBCD) is a tubulin-folding protein essential for the first step of tubulin assembly and regulation of microtubule dynamics (UniProt: Q9BTW9). It captures GTP-bound beta-tubulin and modulates microtubule polymerization through interaction with ARL2, while also promoting epithelial cell detachment and affecting cell junction integrity. TBCD is required for proper mitotic spindle assembly and is involved in neuron morphogenesis.

Mutations in TBCD cause progressive early-onset encephalopathy with brain atrophy and thin corpus callosum (PEBAT; MIM 617193), a neurodevelopmental and neurodegenerative disorder characterized by cortical atrophy, intellectual disability, seizures, and progressive neurological decline (UniProt: Q9BTW9).

TBCD is downregulated in Alzheimer's disease brain tissue compared to age-matched controls (Chaparral AD proteomics). Human post-mortem AD brain proteomics using TMT-labeled, data-dependent acquisition across four subcellular fractions showed a mean log2 fold-change of −0.811 for TBCD, indicating reduced protein abundance in the AD condition.