ADAM15, a disintegrin and metalloproteinase 15, is a transmembrane protein involved in protein ectodomain shedding, cell adhesion, and signaling. It can interact with molecules intra-and extra-cellularly to mediate various cellular functions. ADAM15 affects several important cellular processes, including cell adhesion, degradation of extracellular matrix components, and ectodomain shedding of membrane-bound growth factors, which are relevant to cancer and various inflammatory conditions [3,6].

In disease-related studies, knockdown or knockout of ADAM15 leads to TBEV replication and assembly defects, suggesting its role in the life cycle of tick-borne encephalitis virus [1]. In hepatocellular carcinoma (HCC), ADAM15 is highly expressed, correlated with poor prognosis, and its knockdown promotes apoptosis and suppresses proliferation, migration, and invasion of liver cancer cells [2]. In breast cancer cells, ADAM15 mediates upregulation of Claudin-1 expression [3]. In myocardial infarction, Adam15-/-mice have higher rates of left ventricular rupture, worse left ventricular dysfunction, and reduced collagen cross-linking, indicating ADAM15 is required for optimal collagen cross-linking and scar formation [4]. In prostate cancer, ADAM15 may support disease progression through multiple mechanisms, including promoting metastasis, influencing cell signaling, and angiogenesis [5]. In colorectal tumors, loss of ADAM15 alters the tumor microenvironment, leading to higher immune cell infiltration and cancer cell apoptosis [7]. In pressure overload cardiomyopathy, loss of ADAM15 exacerbates transition to decompensated myocardial hypertrophy and dilation through activation of the calcineurin pathway [8].

In conclusion, ADAM15 is involved in multiple biological processes and plays significant roles in various diseases, such as viral infections, cancers, and heart diseases. Gene knockout mouse models have been crucial in revealing its functions in these specific disease conditions, providing insights into potential therapeutic targets for these diseases.