ADAM9 is a membrane-anchored metalloprotease that functions primarily through its disintegrin domain for cell adhesion and its metalloprotease domain for ectodomain shedding of cell surface proteins 1. The protein participates in diverse physiological processes including cell-cell adhesion, cell-matrix interactions, and may serve as an alpha-secretase for amyloid precursor protein. ADAM9 regulates inflammatory responses and degenerative processes 1. In pathological contexts, ADAM9 is overexpressed in multiple cancer types including non-small cell lung, pancreatic, gastric, breast, ovarian, and colorectal cancers, where it correlates with poor prognosis 2. ADAM9 promotes tumor progression through both proteolytic and non-proteolytic mechanisms; for example, ADAM9 amplification drives pancreatic ductal adenocarcinoma metastasis by downregulating adhesion junctions and upregulating WNT signaling 3. In melanoma, ADAM9-integrin interactions facilitate tumor-stroma cross-talk promoting invasion 4. Beyond cancer, ADAM9 has been implicated in neuroinflammatory pathology; microglia-derived ADAM9 promotes neuronal pyroptosis via the Mad2L2-JNK-caspase-1 pathway in subarachnoid hemorrhage 5. ADAM9 downregulation in knee osteoarthritis synovial fibroblasts occurs through LXA4-mediated suppression of ferroptosis 6. ADAM9 is also associated with cone-rod dystrophy 9. These findings position ADAM9 as a promising therapeutic target; antibody-drug conjugates targeting ADAM9-expressing tumors demonstrate preclinical efficacy 2.