CFAP61 (cilia and flagella associated protein 61) is an essential component of the calmodulin- and radial spoke-associated complex (CSC) required for sperm flagellum assembly and male fertility 1. The protein localizes to the sperm neck and midpiece, where it facilitates radial spoke assembly and axoneme stabilization during spermiogenesis 12. CFAP61 functions within RNA granules formed through liquid-liquid phase separation to regulate translational expression of flagellar genes during spermatid development 3. Biallelic CFAP61 variants cause multiple morphological abnormalities of the flagella (MMAF) phenotype and severe oligoasthenoteratozoospermia (OAT), characterized by disrupted axoneme ultrastructure, absent central pair microtubules, missing radial spokes, and impaired intraflagellar transport 145. Cfap61-deficient mice recapitulate human infertility phenotypes without systemic ciliary dysfunction, revealing an organ-specific mechanism of flagellar stabilization 12. Genetic variants in CFAP61 account for approximately 0.62% of OAT cases in affected populations 5. Clinical interventions using intracytoplasmic sperm injection (ICSI) can achieve successful fertility outcomes despite severe flagellar defects 5. Genome-wide association studies additionally identified CFAP61 variants associated with non-anxiety depression, suggesting pleiotropic effects 6.