CFAP251 (cilia and flagella associated protein 251) is essential for sperm motility and flagellar assembly in mammals. The protein localizes along the sperm flagellum and is a component of the calmodulin- and radial-spoke-associated complex, positioned on the inner surface of peripheral microtubule doublets adjacent to DNAH1 1. CFAP251 functions as a structural component critical for radial spoke assembly, particularly RS3, and appears to regulate cilium motility through its role in axonemal radial spoke organization 23. Loss-of-function mutations in CFAP251 cause multiple morphological abnormalities of flagella (MMAF), leading to sperm with absent, short, coiled, or irregular-caliber flagella 41. Biallelic mutations in CFAP251 have been identified in approximately 5% of Han Chinese men with MMAF, representing a significant genetic cause of male infertility 4. The protein's absence also affects mitochondrial sheath formation during spermatozoon development 1. Proteomic studies have identified CFAP251 as one of several sperm proteins showing deviant abundances in infertile men, confirming its clinical relevance as a biomarker for male fertility assessment 5. These findings establish CFAP251 as a critical component of sperm flagellar function and a clinically significant gene in male reproductive health.