CCNO (cyclin O) is a cell cycle regulator specifically required for multiciliated cell (MCC) differentiation. CCNO acts downstream of MCIDAS to promote centriole amplification and maturation, which are essential for cilia generation 1. Mechanistically, CCNO controls entry into a specialized cell-cycle variant characterized by wave-like expression of canonical and non-canonical cyclins; its absence blocks the G1/S-like transition of this variant and interrupts the centriologenesis transcription program, compromising centriole and cilia production in both brain and respiratory tissues 2. Mutations in CCNO cause reduced generation of motile cilia (RGMC), a subtype of primary ciliary dyskinesia (PCD) characterized by insufficient multiciliated cells in the respiratory and reproductive tracts 12. CCNO mutations represent approximately 5.9% of PCD cases in some cohorts 3. Clinically, CCNO-associated PCD correlates with significantly more severe lung disease (median FEV1 z-score: -3.26), indicating accelerated lung function decline compared to other PCD genotypes 4. Additionally, biallelic CCNO mutations cause infertility due to abnormal gamete transport in reproductive ducts with reduced multiciliated cells; however, assisted reproduction techniques (IVF/ICSI) successfully restore fertility in affected individuals 1.