CCDC32 is a coiled-coil domain protein that functions as a critical regulator of clathrin-mediated endocytosis and ciliogenesis. Mechanistically, CCDC32 acts as a chaperone in adaptor protein complex 2 (AP2) assembly, recognizing AAGAB-stabilized AP2 subcomplexes and serving as a template for sequential recruitment of µ2 and β2 subunits 1. Additionally, CCDC32 stabilizes clathrin-coated pits and drives their invagination through interaction with the α-appendage domain of AP2, with a critical α-helix region (aa78-98) essential for AP2 binding 2. CCDC32 is also required for proper cilia formation in zebrafish and mammalian cells 3. Biallelic loss-of-function mutations in CCDC32 cause cardiofacioneurodevelopmental syndrome (CFNDS), a rare congenital disorder characterized by craniofacial anomalies including bilateral cleft lip and palate, cardiac defects, neurodevelopmental delay, and skeletal abnormalities 34. Clinical features include intellectual disability, hypertelorism, conductive hearing loss, short stature, and hypoplastic corpus callosum 4. The phenotypic overlap with ciliopathies and defects observed in AP2-deficient mice supports a dual pathomechanism involving both ciliary dysfunction and impaired endocytosis 3. CFNDS diagnosis may require RNA-sequencing when conventional genomic approaches fail 5.