ARMC2 (armadillo repeat containing 2) is essential for sperm flagellum axoneme organization and function 1. The protein is specifically required for axonemal central pair complex (CPC) assembly and/or stability 1, as mutations result in absence of CPC proteins SPAG6 and SPEF2 while other axonemal components remain intact 1. Bi-allelic ARMC2 mutations cause multiple morphological abnormalities of the sperm flagella (MMAF), characterized by short, coiled, absent, and irregular flagella 12. This leads to severe astheno-teratozoospermia and male infertility 13. ARMC2 mutations display heterogeneous severity; sperm from Armc2-deficient mice showed moderate embryo developmental impairment compared to other MMAF gene knockouts 4. Notably, ARMC2 is expressed in other ciliary structures, and one patient with ARMC2 mutations exhibited primary ciliary dyskinesia (PCD)-related pulmonary manifestations including recurrent airway infections and rhinosinusitis, expanding the recognized phenotype beyond reproductive dysfunction 5. Clinically, intracytoplasmic sperm injection (ICSI) represents the only viable treatment option for ARMC2-mutated male infertility, with successful pregnancies achieved 65. ARMC2 protein interacts with CEP78, PGAM5, RHOA, FXR1, and SKIV2L2, suggesting involvement in multiple spermatogenesis processes 6.