Tubulin alpha-4A chain

Tubulin alpha-4A chain (TUBA4A) is a core structural protein that forms microtubule dimers with beta-tubulin (UniProt: P68366). As the major constituent of microtubules, it participates in GTP hydrolysis and microtubule polymerization, essential processes for cellular division, intracellular transport, and cytoskeletal organization.

TUBA4A mutations are associated with several neurodegenerative and developmental conditions. UniProt documents links to frontotemporal dementia and/or amyotrophic lateral sclerosis 9 (FTDALS9), spastic ataxia 11 (SPAX11), congenital myopathy 26 (CMYO26), and oocyte maturation arrest 23 (OZEMA23), reflecting its critical role in neuronal integrity and cellular functions across tissues.

In Alzheimer's disease, TUBA4A expression is significantly reduced in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.42; Chaparral AD proteomics). The downregulation was detected across 2 of 4 subcellular fractions in this TMT-labeled quantitative proteomics study, suggesting compromised microtubule dynamics and cytoskeletal integrity as a potential contributor to AD pathology.