CDY2A is a Y-chrY gene encoding a chrY protein with histone acetyltransferase (HAT) activity, primarily functioning in male spermatogenesis. Human CDY and its mouse homolog CDYL exhibit HAT activity with strong preference for histone H4 acetylation 1, a process critical during spermiogenesis when protamines replace histones as DNA-packaging proteins. CDY2A likely arose through retroposition of an autosomal CDYL mRNA ancestor onto the Y chromosome Y primate evolution 2, with subsequent amplification creating multiple copies in the AZFc region 3. The gene shows testis-specific and stage-specific expression, primarily in round and elongating spermatids 34. Functionally, CDY2A exhibits transcriptional corepressor activity and histone reader functions for repressive marks (H3K9me2/3, H3K27me3) [GO annotations], alongside negative regulation of histone crotonylation. Clinically, deletions within the AZFc region containing CDY are detected in 1-10% of infertile men worldwide and associate with oligo- or azoospermia 3. Recent evidence suggests CDY2A promoter variants altering TATA-binding protein affinity correlate with male reproductive potential markers and spermatogenesis disorders 5. However, clear genotype-phenotype relationships remain incomplete, as CDY1 deletion alone does not invariably worsen infertility phenotypes 6.