DPY19L2 encodes a protein essential for proper sperm morphology and male fertility, serving as the primary genetic cause of globozoospermia, a severe form of male infertility characterized by round-headed sperm lacking acrosomes 1. The protein functions during spermatogenesis by facilitating sperm head elongation and acrosome formation, with subcellular localization at the nuclear inner membrane 2. DPY19L2 interacts with FAM209 to maintain the developing acrosome structure 2. Loss of DPY19L2 function results in absence of phospholipase C zeta (PLCζ) in sperm, which is critical for oocyte activation during fertilization 3. Homozygous deletions of the entire DPY19L2 gene account for approximately 61-70% of globozoospermia cases 14, while point mutations such as p.R298C and splice-site variants represent additional causative mechanisms 4. The clinical significance is substantial, as DPY19L2-deficient sperm exhibit severely compromised fertilization potential, with failed calcium oscillation initiation and developmental arrest at metaphase II 3. Patients with DPY19L2 mutations show distinct morphological patterns compared to other globozoospermia subtypes, displaying classic total globozoospermia rather than the mixed phenotypes seen with other genetic causes 5.