ADAM28 is a zinc-dependent metalloproteinase with dual protease and adhesion functions that operates distinctly depending on cellular context. In normal tissues, ADAM28 is primarily expressed by epithelial cells in the bronchus, stomach, and epididymis 1, where it protects cells from C1q-induced apoptosis by binding C1q and suppressing cytotoxicity 1. ADAM28 contains a metalloproteinase domain with catalytic activity and a disintegrin domain that interacts with integrins α4β1, α4β7, and α9β1 2. In cancer contexts, ADAM28 exhibits pro-tumoral functions when expressed by carcinoma cells. It is highly overexpressed in lung, breast, and bladder carcinomas 3, where it promotes proliferation, survival, migration, and metastasis through proteolytic cleavage of substrates including insulin-like growth factor binding protein-3 (IGFBP-3), von Willebrand factor (vWF), and connective tissue growth factor (CTGF), while also enhancing PSGL-1/P-selectin-mediated cell adhesion 34. SOX4, an epithelial-mesenchymal transition inducer, directly transactivates ADAM28 expression, suggesting involvement in invasion 5. Conversely, host-derived ADAM28 in the tumor microenvironment exerts protective effects, as ADAM28 knockout mice show accelerated lung colonization and impaired T cell responses 6. Additionally, ADAM28 acts as a novel sheddase of tumor necrosis factor-α and correlates with metabolic syndrome parameters 7.