Ttll7, a member of the tubulin tyrosine ligase-like (TTLL) protein family, is a mammalian beta-tubulin polyglutamylase. Tubulin polyglutamylation is a post-translational modification of microtubules, which is crucial for cytoskeletal functions, especially in neurons. It may be involved in regulating microtubule-interacting proteins, and plays an important role in the growth of MAP2-positive neurites [2].

Ttll7 knockout mouse models have been used to study its functions. Ttll7 knockout mice showed abnormal behaviors, and MALDI-IMS analyses indicated an increase in glutamate in their brains, suggesting that tubulin polyglutamylation by Ttll7 acts as a glutamate pool in neurons and modulates other glutamate-related amino acids [1]. In addition, deletion of Ttll7 did not prevent the degeneration of Purkinje cells and myelinated axons in peripheral nerves in mice lacking the deglutamylase CCP1, and loss of Ttll7 had no effect on mitochondria motility in neurons, which helps to clarify the distinct roles of Ttll7-mediated polyglutamylation compared to that of other enzymes like Ttll1 [3].

In conclusion, Ttll7 is essential for regulating microtubule-related functions in neurons, especially through its role in beta-tubulin polyglutamylation. The use of Ttll7 knockout mouse models has provided insights into its role in glutamate regulation in the brain and its distinct contribution to neurodegeneration-related processes compared to other polyglutamylases. This research helps to understand the complex mechanisms of neuronal function and neurodegenerative diseases.