TUBB3, encoding the neuronal-specific β-tubulin isotype III, is a crucial component of neuronal microtubules [1]. It is essential for neuronal migration, axon growth and guidance, which rely on precise control of microtubule dynamics and microtubule-based cargo transport [1]. The protein is expressed throughout the life of central and peripheral neurons, highlighting its importance in the nervous system.

Human pathogenic TUBB3 missense variants can lead to altered TUBB3 function, resulting in errors in cranial and central axon growth and guidance, or cortical neuronal migration and organization [1]. In vitro and mouse models have shown that loss-of-function and missense variants can alter microtubule dynamics and microtubule-kinesin interactions [1].

In prostate cancer, TUBB3 is highly expressed in bone-metastatic PCa and its depletion reverses anoikis resistance, inhibits cell invasion, migration and EMT process [2]. TUBB3 knockdown also re-sensitizes docetaxel-and cabazitaxel-resistant cells to these drugs, indicating its role in drug resistance [3]. In gallbladder cancer, TUBB3 promotes cancer cell growth and invasion through the Akt/mTOR signal pathway [4].

In conclusion, TUBB3 is vital for normal neuronal development due to its role in microtubule-related functions. Model-based research, especially with mouse models, has revealed its significance in various disease conditions such as neurological disorders and multiple cancers, providing insights into potential therapeutic targets for these diseases.