DNHD1 (dynein heavy chain domain 1) is essential for sperm flagellar axoneme assembly and function. The protein localizes throughout normal sperm flagella and serves as a critical structural component of the inner dynein arm complex, which generates ATP-dependent minus-end-directed microtubular movement 1. DNHD1 functions to maintain central pair microtubule organization and mitochondrial sheath integrity within the flagellar midpiece 12. Bi-allelic DNHD1 variants cause asthenoteratozoospermia and multiple morphological abnormalities of the sperm flagellum (MMAF), characterized by reduced sperm motility and severe flagellar defects including central pair microtubule deficiency and mitochondrial sheath malformations 12. Male infertility is the primary clinical consequence, with knockout mouse models demonstrating complete reproductive failure 1. However, intracytoplasmic sperm injection can overcome the fertility barrier in affected individuals 1. DNHD1 variants account for approximately 1.6% of asthenoteratozoospermia cases in sequenced populations 1. DNHD1 has been proposed as a candidate gene for early fetal developmental anomalies 3, and DNA methylation patterns at the DNHD1 locus may contribute to left ventricular cardiac structural function 4. The gene has been identified in various cancer genomic analyses, though its role in malignancy remains unexplored.