Precise regulation of microtubules is essential for brain development and function. Deregulation of microtubules has been linked to abnormal neural development and is associated with a range of neurodevelopmental and neurodegenerative disorders, including autism spectrum disorder, schizophrenia and Alzheimer’s disease. Among the mechanisms that modulate microtubule function, tubulin posttranslational modifications seem to play a critical role. In neurons, tubulin polyglutamylation influences processes in both developing and mature cells. In the presentation, I will focus on our recent findings demonstrating how dysregulated tubulin polyglutamylation impairs the refinement of neural connectivity in vivo, in both the central and peripheral nervous systems, and how it contributes to neurodegeneration in the adult brain.