ADAM10 is a membrane-anchored metalloprotease that functions as the primary α-secretase for amyloid precursor protein (APP) cleavage, generating neuroprotective sAPPα and preventing Aβ accumulation 1. The enzyme requires tetraspanin binding (e.g., Tspan15) to relieve autoinhibition and position its active site approximately 20 Å from the plasma membrane for substrate cleavage 2. ADAM10 catalyzes ectodomain shedding of multiple transmembrane proteins including Trop-2, whose cleavage activates cancer growth and metastasis across multiple tumor types 3. The enzyme also processes NOTCH2 to regulate Wnt pathway transcription in colorectal cancer 4. Regulation by the GDE2-RECK axis controls APP processing; elevated membrane RECK in Alzheimer's disease impairs ADAM10 function 1. Beyond cancer, ADAM10 mediates pathogenic endothelial injury during bacterial sepsis by facilitating toxin-induced damage, as shown with S. aureus and P. aeruginosa 5. In myocardial infarction, ADAM10-mediated CX3CL1 shedding drives excessive neutrophil recruitment and tissue damage; ADAM10 inhibition improves survival 6. ADAM10 gene polymorphisms associate with hepatocellular carcinoma progression and metastasis risk 7. These findings position ADAM10 as a therapeutic target across Alzheimer's disease, cancer, sepsis, and cardiovascular disease.