WFDC8 encodes a whey acidic protein four-disulfide core domain protein involved in male reproductive function. WFDC8 is expressed in epididymal epithelial cells, specifically in both principal and clear cells 1, and is transferred to maturing spermatozoa via epididymosomes—extracellular vesicles released by the epididymis that contribute to post-testicular sperm maturation 1. Functionally, WFDC8 is critical for male fertility; CRISPR/Cas9-based deletion studies demonstrated that males lacking WFDC8 (as part of multi-gene deletions including Wfdc6a and Eppin) exhibit sterility due to arrest of spermatogenesis at the round spermatid stage, preventing formation of elongated spermatids 2. Evolutionarily, WFDC8 has been subject to adaptive selection pressures; the gene shows signatures of short-term balancing selection in European populations 3 4, with putative selection-targeted variants such as 44A (rs7273669A) potentially regulating gene expression 4. The WFDC locus broadly participates in antimicrobial, immune, and reproductive homeostasis 3. These findings indicate WFDC8 has important clinical implications for understanding male infertility and identifying potential therapeutic or contraceptive targets.