A bioinformatics-based analysis has identified TMEM107 as a candidate transition zone (TZ) ciliary gene that is mutated in oral–facial–digital and Joubert syndromes. Functional analyses performed in C. elegans showed that TMEM107 contributes to ciliary composition and function in a redundant manner with NPHP-4, and regulates cilium integrity, TZ docking, and assembly of membrane-to-microtubule (Y-link) connectors. TMEM107 localizes to layer three of the 'MKS module' in the TZ, where it organizes recruitment of ciliopathy proteins.