SPEF2 (sperm flagellar and cilia associated 2) is essential for proper sperm flagellar development and male fertility. The protein plays a critical role in axoneme assembly, particularly in forming the central pair complex of sperm flagella 12. SPEF2 functions as an adapter protein for dynein-mediated transport during spermatogenesis, facilitating localization of intraflagellar transport protein IFT20 to the manchette, which is crucial for normal sperm head morphology and flagellar development 1. Loss-of-function mutations in SPEF2 cause multiple morphological abnormalities of the sperm flagella (MMAF), characterized by absent, short, coiled, or irregular flagella with disrupted axonemal structures and mitochondrial sheath defects 21. Interestingly, SPEF2 mutations also cause primary ciliary dyskinesia (PCD) symptoms including recurrent respiratory infections, demonstrating differential roles in sperm flagella versus respiratory cilia 34. In respiratory cilia, SPEF2 is required for central pair complex formation, and its absence can be used diagnostically for detecting PCD with central pair defects 5. Clinically, SPEF2-related male infertility can be successfully treated with intracytoplasmic sperm injection (ICSI), with favorable pregnancy outcomes reported 64.