TTLL11 is a polyglutamylase enzyme that catalyzes ATP-dependent polyglutamylation of tubulin proteins, preferentially elongating polyglutamate chains rather than initiating them 1. The enzyme exhibits a unique bipartite microtubule recognition strategy, engaging adjacent protofilaments to extend primary polypeptide chains of both α- and β-tubulin 1. Beyond tubulin modification, TTLL11 also polyglutamylates non-tubulin substrates like Dishevelled 3 (DVL3) through carboxy-terminal polyglutamylation, affecting protein phase separation and Wnt signaling 2. TTLL11 is essential for proper chromosome 9 during mitosis, with reduced levels compromising segregation fidelity and causing chromosome 9 3. The enzyme plays critical roles in neuronal development by regulating α-tubulin polyglutamylation, which restricts neurite branching when working synergistically with doublecortin 4. Clinically, TTLL11 mutations are associated with idiopathic scoliosis through ciliary defects 5, and genetic variants correlate with sustained attention performance and ADHD susceptibility 6. The gene is systematically downregulated in cancer cells, linking reduced TTLL11 expression to aneuploidy and chr9 instability 3. TTLL11 is also involved in oocyte meiosis and drug response variability in Kawasaki disease 78.