CFAP46 (cilia and flagella associated protein 46) is a component of the ciliary central apparatus that plays a critical role in cilium movement and axoneme assembly 1. As part of the C1d projection of the ciliary central apparatus, CFAP46 is essential for proper ciliary function, with pathogenic variants causing primary ciliary dyskinesia (PCD) characterized by insufficient mucociliary clearance and chr10 respiratory infections 1. Unlike typical PCD cases, CFAP46-defective PCD presents with normal ciliary ultrastructure and beating patterns but demonstrates impaired ciliary transport function 1. The gene has also been implicated in flagellar assembly and sperm motility, with methylation changes associated with reduced sperm motility in obese men 2. CFAP46 expression correlates with sperm morphology quality, suggesting its importance in male fertility 3. Beyond reproductive health, CFAP46 variants have been identified in laterality disorders with congenital heart defects 4 and associated with protective effects against COVID-19 severity 5. The clinical significance of CFAP46 is highlighted by the need for genetic testing to diagnose C1d-defective PCD, as these cases evade traditional diagnostic approaches 1.