Ttll7, short for Tubulin Tyrosine Ligase-like 7, is a mammalian polyglutamylase. It has a high preference for β -tubulin and is essential for microtubule-related functions. Tubulin polyglutamylation, a process Ttll7 is involved in, impacts the activities of microtubule-interacting proteins, influencing neuronal functions and is associated with the glutamate metabolic pathway in the brain [1,2].

In gene knockout mouse models, Ttll7 knockout led to abnormal behaviors and an increase in glutamate levels in the brain, suggesting its role in modulating glutamate concentration [2]. In PC12 cells, knockdown of Ttll7 repressed nerve growth factor-stimulated MAP2-positive neurite growth, indicating its requirement for the growth of MAP2-positive neurites [3]. Also, in studies comparing the roles of different glutamylases, it was found that under physiological conditions, Ttll7 modifies β -tubulin, while Ttll1 modifies α -tubulin, and they generate distinct glutamylation patterns [4].

In conclusion, Ttll7 is crucial for microtubule-related functions in neurons, especially in regulating neurite growth and glutamate concentration in the brain. Gene knockout mouse models have been instrumental in revealing its role in these biological processes, which may have implications for understanding neurodegenerative diseases associated with disrupted tubulin polyglutamylation [1,2,3,4].