ADAM2 is a membrane-anchored metalloprotease-family protein with specialized roles in male reproduction and emerging immunological functions. In the testis, ADAM2 is specifically expressed in germ cells 1 and forms multi-protein complexes critical for sperm function 2. The protein contains multiple functional domains including a disintegrin-like domain with an FEE binding tripeptide capable of integrin recognition 3, enabling sperm-egg interactions during fertilization 2. However, ADAM2 expression differs markedly across species: while present on mature sperm in mice and monkeys, it localizes to testis but not mature sperm in humans 4, suggesting divergent reproductive mechanisms. ADAM2 serves as a biomarker for sperm quality in male factor infertility, with reduced levels correlating with poor chr8 maturation and embryo quality 5. Unexpectedly, ADAM2 functions as an oncogene in lung cancer by suppressing interferon and TNF signaling, reducing tumor antigen presentation and immune checkpoint inhibitor expression 6. Notably, despite its cancer-testis antigen classification, ADAM2 is not expressed in lung or breast cancers and cannot be induced by epigenetic modulation, limiting its utility as an immunotherapy target 7.