TBCD (tubulin folding cofactor D) is a chaperone protein essential for tubulin heterodimer assembly and microtubule dynamics regulation. TBCD functions as a cofactor in the post-chaperonin tubulin folding pathway, capturing GTP-bound β-tubulin and facilitating proper α/β-tubulin complex assembly 1. As a GTPase-activating protein for ARL2, TBCD's interaction with β-tubulin is regulated via ARL2 binding, which also antagonizes TBCD-induced epithelial cell detachment and tight junction disassembly 1. TBCD localizes to centrosomes and midbodies during the cell cycle, where it participates in centriologenesis, spindle microtubule organization, and cytokinesis 2. Proper TBCD function is critical for mitotic spindle assembly and neuron morphogenesis 2. TBCD expression is detected in human gametes, with differential localization in sperm (middle region and tail) versus oocytes (cytosolic), suggesting roles in gametogenesis-associated cytoskeletal changes 3. Mutations in TBCD cause progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT), a severe neurodegenerative tubulinopathy presenting with developmental regression, epilepsy, and microcephaly within the first year of life 45. Disease severity reflects TBCD's critical role in neuronal microtubule dynamics during development.