DNAH8 encodes a dynein axonemal heavy chain that functions as a force-generating component of outer dynein arms (ODAs) in sperm flagella 1. It produces force toward minus ends of microtubules through ATPase activity, with the power stroke occurring upon ADP release 1. DNAH8 is essential for sperm flagellar assembly and motility 1. Bi-allelic DNAH8 variants cause multiple morphological abnormalities of the sperm flagella (MMAF), a severe asthenoteratozoospermia characterized by immotile spermatozoa with malformed flagella 12. Loss-of-function mutations lead to absent or markedly reduced DNAH8 staining and reduced expression of associated protein DNAH17 13. Electron microscopy reveals highly aberrant sperm flagellar ultrastructure in affected individuals 1. DNAH8 variants are identified in approximately 2.2% of MMAF-affected men 1 and contribute to spermatogenic failure 46 4. Dnah8-knockout mice exhibit typical MMAF phenotypes and sterility 1. Clinically, intracytoplasmic sperm injection using affected spermatozoa achieves successful pregnancy outcomes, bypassing the flagellar dysfunction 15. Additionally, DNAH8 variants are enriched in hypospadias cases, with Dnah8 knockout mice showing decreased testosterone levels affecting urethral development 6.