ADAM8 is a membrane-anchored metalloproteinase-disintegrin primarily expressed in immune cells including monocytes, neutrophils, eosinophils, and dendritic cells 1. Its primary function involves ectodomain shedding of membrane proteins, notably CD23 and L-selectin 1, and regulation of leukocyte extravasation and migration 2. ADAM8 operates through both proteolytic and non-proteolytic mechanisms: as a sheddase cleaving extracellular substrates, and via its disintegrin domain binding integrins (particularly β1-integrin) to activate intracellular signaling pathways including FAK, ERK1/2, and AKT 3. In cardiac macrophages, ADAM8 phosphorylates ANXA2 to inhibit autophagy and suppress angiogenesis following myocardial infarction 4. In neuroinflammation, ADAM8 forms complexes with Fra-1 to activate Map3k4/MAPK signaling in microglia 5. ADAM8 dysregulation associates with multiple pathologies: elevated expression correlates with poor outcomes in breast, pancreatic, and brain cancers through enhanced invasiveness and chemoresistance 3; increased plasma levels predict leukemia risk 6; and upregulation drives allergic airway inflammation in asthma 1. As a 'signaling hub,' ADAM8 coordinates immune recruitment and tumor microenvironment communication, making it a promising therapeutic target 7.