CFAP58 is a testis-enriched cilia and flagella-associated protein essential for sperm axoneme assembly and flagellar development 1. The protein localizes predominantly to the sperm midpiece and functions as a cargo stabilizer in the intra-flagellar transport pathway, interacting with IFT88 and CCDC42 2. CFAP58 is required for central pair (CP) microtubule assembly and organization of axoneal ultrastructure proteins including SPAG6, SPEF2, and mitochondrial sheath components 31. Additionally, CFAP58 modulates primary cilium elongation through Notch signaling pathway modulation 4. Biallelic loss-of-function CFAP58 mutations cause multiple morphological abnormalities of sperm flagella (MMAF), a severe form of male infertility characterized by flagellar defects, axonemal malformations, and abnormal sperm head shaping 513. CFAP58 deficiency increases spermatozoa apoptosis and results in infertility in mouse models 2. Genetic variants in the CFAP58 promoter are associated with reduced semen quality in cattle, including elevated sperm deformity rates 2. CFAP58 mutations have been identified in multiple unrelated consanguineous families with MMAF, establishing CFAP58 as a pathogenic gene for this condition 5. Intracytoplasmic sperm injection (ICSI) represents an effective assisted reproductive treatment for male infertility caused by CFAP58 mutations 5. Additionally, rare CFAP58 variants associate with telomere length and increased cancer mortality risk 6.