ZCWPW2 is a histone methylation reader protein that recognizes H3K4 methylation marks with binding preference for H3K4me3 > H3K4me2 > H3K4me1 > H3K4me0 1. The protein's CW domain forms a methyllysine recognition cage through conserved tryptophan residues that interact with trimethylated lysine-4 on histone H3 1. Mechanistically, ZCWPW2 functions as an essential component of meiotic recombination by forming a complex with ZCWPW1 and interacting with recombination-associated proteins 2. This complex recognizes dual H3K4me3 and H3K36me3 marks deposited by PRDM9 at recombination hotspots, while also binding promoter regions to regulate meiotic transcription 2. The ZCWPW1-ZCWPW2 complex enhances lactylation of recombination proteins through interaction with LDHA and EP300, stabilizing their abundance 2. Clinically, ZCWPW2 deficiency causes meiotic recombination defects including impaired homologous chromosome 3 and defective DNA double-strand break repair, leading to infertility 2. Additionally, ZCWPW2 genetic variants associate with increased glycosylated hemoglobin in diabetic nephropathy 3. Phylogenetic analysis reveals tight coevolution of ZCWPW2 with PRDM9 across vertebrates, suggesting its role as a key meiotic recombination interactor 4.