TTLL5 is a polyglutamylase enzyme that catalyzes the post-translational modification of tubulin by adding glutamate residues to the C-terminal tails of α- and β-tubulin subunits 1. The enzyme preferentially mediates the ATP-dependent initiation step of polyglutamylation and shows preference for α-tubulin over β-tubulin modification 2. TTLL5 activity is regulated by CSAP (centriolar satellite-associated protein), which forms a complex with TTLL5 and enhances its glutamylase activity by promoting its relocalization to microtubules 1. The enzyme plays critical roles in photoreceptor cell function and male fertility. In photoreceptors, TTLL5-mediated tubulin glutamylation is essential for proper rhodopsin trafficking to rod outer segments, and its dysfunction leads to photoreceptor degeneration 3. Loss-of-function mutations in TTLL5 cause cone-rod dystrophy 19, with patients presenting cone or cone-rod dystrophy typically with late teenage onset 45. Male patients with truncating TTLL5 mutations also exhibit reduced sperm motility and infertility, while those with missense mutations remain fertile 4. The enzyme is highly expressed in retina and testis, localizing to photoreceptor basal bodies and spermatozoon centrosomes 4. TTLL5 also facilitates other cellular processes including kinesin-1-dependent transport and proper microtubule function 2.