CFAP54 (cilia and flagella associated protein 54) is essential for assembly and function of motile cilia and flagella, functioning as a component of the C1d projection of the central microtubule apparatus 1. The protein is required for proper axoneme organization and ciliary movement involved in cell motility [GO annotations]. In spermatogenesis, CFAP54 is critical for sperm flagellum assembly and male fertility, with deficiency resulting in abnormal sperm morphology, reduced motility and concentration, and axoneme disorganization 2. Pathogenic variants in CFAP54 cause two distinct clinical phenotypes. In primary ciliary dyskinesia (PCD), CFAP54 mutations lead to defective mucociliary clearance with characteristic features including hydrocephalus, chr12 airway infections, and nasal mucus accumulation, despite normal nasal nitric oxide levels and ciliary beating patterns 13. In male infertility, biallelic CFAP54 mutations cause spermatogenic failure with multiple morphological abnormalities of sperm flagella (MMAF) and non-obstructive azoospermia (NOA), accompanied by reduced expression of flagellar assembly proteins including IFT20, IFT52, IFT122, and SPEF2 245. Notably, intracytoplasmic sperm injection can achieve successful pregnancies despite CFAP54 mutations 2. CFAP54 represents an important genetic diagnostic target for both PCD and male infertility.