IQCN (IQ motif containing N) is essential for male fertility and successful fertilization 1. The protein functions as a calmodulin-binding regulator that controls microtubule nucleation during manchette assembly in elongating spermatids 12. IQCN interacts with calmodulin to regulate phosphorylation of downstream calmodulin-binding proteins involved in male gamete generation and cytoskeletal organization 2. Loss-of-function mutations in IQCN cause autosomal-recessive male infertility characterized by total fertilization failure (TFF) 3. Affected individuals exhibit abnormal sperm morphology, including defective acrosome structures and impaired flagellar assembly with irregular '9 + 2' microtubule organization, resulting in reduced sperm motility and fertilization capacity 14. Even intracytoplasmic sperm injection (ICSI) fails without assisted oocyte activation 5. IQCN mutations are associated with Spermatogenic failure 78 6. Intriguingly, ICSI combined with assisted oocyte activation can overcome IQCN-associated TFF, offering a therapeutic option for affected couples 1. The identification of IQCN variants provides important genetic markers for diagnosing unexplained male infertility and guides personalized clinical interventions.