C2CD3 is a centriolar protein essential for primary cilium formation and centriole structure. As a positive regulator of centriole elongation 1, C2CD3 functions as a luminal ring organizer with 9-fold radial symmetry within the centriole's distal end, where it acts as an architectural hub connecting the centriolar lumen to distal appendages 2. C2CD3 directly promotes recruitment of distal appendage proteins including CEP164, CEP83, and others required for ciliary anchoring 1, and interacts with CEP120 and Talpid3 to enable appendage assembly 3. At the molecular level, C2CD3 scaffolds the DISCO complex (containing MNR) and stabilizes the luminal ring network composed of SFI1, centrin-2, CEP135, and NA14 2. Beyond centriole biology, C2CD3 is critical for Sonic Hedgehog signaling and GLI3 proteolytic processing 4, 5. Biallelic C2CD3 mutations cause orofaciodigital syndrome 14 (OFD14), characterized by severe microcephaly, cerebral malformations, and skeletal dysplasia 6, 1. Hypomorphic variants can present with isolated nephronophthisis featuring shortened cilia and impaired SHH signaling 5. C2CD3 also exhibits tissue-specific isoforms with critical roles in craniofacial development 7, establishing it as a central organizer of ciliary and developmental signaling.