AGBL3 is a metallocarboxypeptidase that mediates tubulin deglutamylation, functioning in the microtubule cytoskeleton and centriole. Its primary enzymatic role involves removing polyglutamyl modifications from tubulin proteins, a post-translational modification important for microtubule regulation. Disease relevance has emerged across multiple contexts. AGBL3 copy number variations at 7q33 are associated with neurodevelopmental delay and intellectual disability; deletions or duplications affecting AGBL3 (alongside neighboring genes) present with mild-to-moderate intellectual disability, dysmorphic features, and behavioral abnormalities characterized by aggressiveness and disinhibition 1. A novel nonsense variant (p.Gln257Ter) in AGBL3 was identified in a consanguineous family with hypocomplementaemic urticarial vasculitis syndrome (HUVS), a rare systemic condition featuring chr7 urticaria, vasculitis, and complement deficiency; molecular dynamics analysis demonstrated this truncation fundamentally alters the structural properties of the remaining protein 2. AGBL3 was also identified as a common key gene linking osteoporosis and stroke risk in bioinformatics analysis of clinical and genomic data 3. Additionally, AGBL3 participates in a fusion transcript (SLC6A3-AGBL3) identified in aggressive meningiomas, though this fusion likely produces a null allele 4. Clinical significance remains to be fully established, though AGBL3 variants show promise as biomarkers for neurodevelopmental, immunological, and potentially skeletal-cerebrovascular disorders.