ADAM8

ADAM8 (A Disintegrin and Metalloproteinase 8) is a transmembrane metalloprotease and sheddase that regulates cell-cell and cell-matrix interactions through ectodomain shedding of membrane-associated proteins, with particularly high expression in myeloid and other immune cell populations^[1][2]. Mechanistically, ADAM8 functions as a signaling hub that coordinates extracellular, intracellular, and intercellular communication, thereby influencing inflammatory responses, leukocyte migration, and tissue remodeling processes^[3][4]. Through proteolytic processing of substrates involved in adhesion and immune regulation, ADAM8 promotes chemotaxis, transendothelial migration, and extracellular matrix interaction in inflammatory settings^[2][3]. In disease models, elevated ADAM8 expression has been associated with chronic inflammation, allergic airway disease, neuroinflammatory conditions, and multiple invasive cancers, where it contributes to tumor cell motility, invasion, and tumor-immune cell crosstalk^[2][4][5]. Compared with related ADAM family proteases, ADAM8 possesses a relatively restricted validated substrate repertoire, undergoes autocatalytic prodomain removal rather than classical furin-dependent activation, and exhibits catalytic activity that is largely insensitive to tissue inhibitors of metalloproteinases (TIMPs), highlighting distinct regulatory features within the ADAM family^[3]. For experimental applications, ADAM8 has emerged as a therapeutic target, and inhibitory strategies including peptide inhibitors and RNA aptamers have demonstrated utility in preclinical models of inflammatory disease and cancer, supporting its value for mechanistic and translational research^[3][6].