CFAP44 (cilia and flagella associated protein 44) is a flagellar protein essential for sperm axoneme organization and function 1. Located between doublet microtubules 5-6 and the paraflagellar rod 1, CFAP44 possesses peptidase activity and participates in microtubule cytoskeleton organization through protein-protein interactions 2. The protein regulates cellular processes including microtubule formation via cleavage of β-tubulin and the bacterial homolog FtsZ 2. Biallelic mutations in CFAP44 cause multiple morphological abnormalities of the sperm flagella (MMAF), characterized by absent, short, coiled, or bent flagella that severely impair sperm motility 34. CRISPR/Cas9-generated Cfap44-deficient male mice exhibit MMAF phenotypes and infertility, while females remain fertile, confirming testis-specific functional requirements 4. Reduced CFAP44 expression correlates with asthenozoospermia and terato-asthenozoospermia, with positive associations between CFAP44 levels and normal sperm morphology and motility 56. Environmental insults like fluoride exposure downregulate CFAP44 expression, disrupting the "9+2" microtubule axonemal structure 7. Sperm from Cfap44-deficient males show minimal developmental impairment when used for intracytoplasmic sperm injection 8, representing the primary treatment option for CFAP44-associated male infertility.