ZCWPW1 (zinc finger CW-type and PWWP domain containing 1) functions as a dual histone methylation reader specific for PRDM9-catalyzed marks H3K4me3 and H3K36me3 12. The protein facilitates repair of PRDM9-induced meiotic double-strand breaks and shows tight evolutionary coevolution with PRDM9 across vertebrates, suggesting a key role in recombination machinery recruitment or DNA repair 3. ZCWPW1 is essential for male fertility and spermatogenesis, required for meiosis prophase I progression specifically in male germ cells. Clinically, ZCWPW1 variants cause male infertility. A homozygous missense mutation (c.1064C>T, p.P355L) was identified in an infertile patient with oligoasthenoteratozoospermia, characterized by sperm head defects and elevated DNA fragmentation 4. Mutations in ZCWPW1 are classified among genes causing amorphous sperm head morphology 5. Addditionally, ZCWPW1 variants associate with late-onset Alzheimer's disease (LOAD) risk. The rs1476679 polymorphism significantly associates with LOAD in Han Chinese populations and meta-analyses of 82,525 individuals, with the C allele conferring protective effects 6. However, within the ZCWPW1 locus, neighboring genes PILRB and GATS show stronger eQTL associations with AD status and elevated expression in microglia, suggesting complex locus architecture 7.