TUBA3D encodes tubulin alpha 3d, a core structural protein component of microtubules 1. As part of alpha-beta tubulin heterodimers, TUBA3D contributes to microtubule polymerization through GTP binding and hydrolysis, with stabilizing caps forming at microtubule ends [UniProt]. The protein is highly expressed in corneal tissue and plays a critical role in maintaining corneal structural integrity. Mutations in TUBA3D cause keratoconus (KC), a degenerative corneal disease characterized by progressive stromal thinning 1. De novo and inherited mutations identified include nonsense mutations (c.31 C>T, p.Gln11stop) and frameshift variants (c.201insTT). Mutant TUBA3D proteins are unstable and trigger pathogenic corneal remodeling through increased matrix metalloproteinase (MMP1) and urokinase plasminogen activator (UPA) expression, combined with elevated oxidative stress in corneal fibroblasts 1. These changes reduce extracellular matrix deposition, directly causing characteristic KC stromal thinning. Beyond keratoconus, TUBA3D exhibits altered expression in multiple cancer contexts. Bioinformatics studies identified TUBA3D as a candidate autophagy-related gene in cancer 2 and as a prognostic biomarker in breast cancer risk models 34. TUBA3D expression is also associated with left atrial appendage thrombus formation in atrial fibrillation 5 and correlates with dilated cardiomyopathy-induced heart failure pathways 6. These findings suggest TUBA3D functions extend beyond cytoskeletal organization to disease pathogenesis across multiple organ systems.