TTLL7 is a tubulin polyglutamylase enzyme that catalyzes the addition of polyglutamate chains to the C-terminal tail of tubulin, with high specificity for β-tubulin over α-tubulin 12. The enzyme mediates both ATP-dependent initiation and elongation steps of the polyglutamylation reaction, utilizing a tripartite microtubule recognition strategy involving its catalytic core and a flexible cationic domain for substrate positioning 2. TTLL7 is predominantly expressed in the nervous system and plays a critical role in neuronal development and function 1. The enzyme is essential for MAP2-positive neurite growth, as demonstrated by knockdown studies in PC12 cells that showed impaired nerve growth factor-stimulated neurite development 1. TTLL7 localizes to the somatodendritic compartment of neurons and its expression increases during neuronal differentiation 1. Beyond its role in neurite growth, TTLL7 participates in hematopoietic stem cell regulation through glutamylation of deubiquitinase BAP1, affecting its stability and downstream gene expression 3. Additionally, TTLL7 contributes to brain glutamate homeostasis, with knockout mice showing altered amino acid metabolism 4. Disease associations include roles in glioblastoma prognosis and narcolepsy pathogenesis 56.