TTLL3 (tubulin tyrosine ligase-like 3) is a monoglycylase that catalyzes the addition of single glycine residues to specific glutamate residues within the C-terminal tails of alpha- and beta-tubulin 1. The enzyme preferentially glycylates beta-tubulin but shifts its preference toward alpha-tubulin as beta-tubulin glutamylation increases, competing with polyglutamylases for overlapping modification sites 1. This competition creates an anticorrelation between glycylation and glutamylation reactions that is part of a combinatorial "tubulin code" regulating microtubule interactions with cellular effectors 1. TTLL3 is essential for microtubule glycylation in primary cilia, where it works with TTLL8 to maintain cilium stability and prevent degeneration 23. The enzyme is the only tubulin glycylase expressed in the human retina, where it is critical for preventing photoreceptor cilium degeneration 3. In colon epithelium, TTLL3-mediated primary cilia maintenance controls epithelial cell proliferation; TTLL3 knockout mice show reduced primary cilia numbers, increased cell division, and strongly promoted tumor development 2. Decreased TTLL3 expression is associated with human colorectal carcinoma development 2. Additionally, TTLL3 glycylates sperm flagella to regulate axonemal dynein motor activity, controlling male fertility [UniProt]. Rare TTLL3 mutations have been identified in persistent pulmonary hypertension of the newborn patients 4.