AXDND1 is a testis-enriched gene essential for male fertility that functions primarily in regulating spermatogonial commitment and spermiogenesis 12. The protein localizes to the manchette, a dynamic cytoplasmic structure critical for spermatid development, where it regulates manchette dynamics, spermatid head shaping, and sperm flagellum assembly 2. AXDND1 functions as an atypical dynein complex-related protein involved in protein and vesicle transport 1. Loss of AXDND1 causes male infertility through multiple mechanisms: it disrupts the balance between self-renewing and differentiation-committed spermatogonial populations, leading to progressive germ cell depletion and testicular failure 12. Additionally, AXDND1-deficient sperm exhibit severe morphological abnormalities including abnormal axoneme structure with ectopic vesicles, deficient outer dense fibers, and microtubule doublet disorganization, resulting in sperm immotility 12. Pathogenic AXDND1 variants have been identified in infertile men with non-obstructive azoospermia and multiple morphological abnormalities of sperm flagella (MMAF), with frameshift mutations causing complete loss of AXDND1 expression and absent central pair microtubules in flagella 23. These findings establish AXDND1 as critical for maintaining both the spermatogonial stem cell pool and producing motile sperm.