CEP76 is a centrosomal protein with multifaceted roles in cell cycle regulation and ciliary biology. Structurally, CEP76 contains a transglutaminase-like peptidase domain and C2 domains involved in protein-protein interactions 1, and possesses catalytically active peptidase-like domains 2. Primary functions include restricting centriole duplication to once per cell cycle by suppressing PLK1 activation in the cytoplasm during mitosis 3, with phosphorylation at S83 by CDK2 and acetylation at K279 serving as opposing post-translational modifications that regulate this inhibitory capacity 4. Beyond centriole regulation, CEP76 functions at the centrosome-cilium interface, regulating ciliary assembly, intraflagellar transport, and transition zone architecture 5. In male germ cells, CEP76 controls selective protein entry into the ciliary compartment and dictates annulus positioning 6. Clinically, biallelic CEP76 variants cause a spectrum of ciliopathies presenting with neurodevelopmental, ocular, and multisystem features, characterized by impaired cilium formation and disrupted transition zone architecture 5. Disease-associated variants are pathogenic and impair the protein's ability to suppress centriole amplification 4. Additionally, CEP76 variants identified in placental DNA methylation studies associate with altered offspring cognitive function, suggesting developmental significance 7.