TUBB4B encodes β4B-tubulin, a major constituent of microtubules that polymerizes with α-tubulin heterodimers through GTP-dependent mechanisms [UniProt]. TUBB4B has critical, non-redundant roles in organizing organelle-specific microtubule structures, particularly in ciliary and auditory systems 1. In the inner ear, TUBB4B is essential for maintaining organized microtubule networks in cochlear pillar cells that provide mechanical support for auditory transmission, and for developing motile cilia in middle ear epithelial cells 2. Notably, TUBB4B shows functional specificity—it is essential for hearing but not vision in mice, with β6-tubulin providing compensatory mechanisms in retinas 2. Pathogenic variants in TUBB4B cause ciliopathies and tubulinopathies manifesting as sensorineural hearing loss and inherited retinal dystrophy (IRD) 13. Hotspot mutations at codons Arg390 and Arg391 differentially affect TUBB4B-α-tubulin heterodimer stability and affinity, correlating with distinct retinal phenotypes 3. Arg391 substitutions cause more severe retinal disease with peripheral lesions, while Arg390 variants associate with pericentral retinitis pigmentosa 34. Beyond sensory systems, TUBB4B regulates CD4+ T cell differentiation; TUBB4B downregulation in Behçet's uveitis correlates with increased Th17/Th1 responses, suggesting therapeutic potential 5. These findings establish TUBB4B as an isotype-specific regulator of microtubule function in specialized cellular contexts.