ADAMTS proteases in extracellular vesicles: emerging mediators of extracellular matrix dynamics and disease progression

Recent advances highlight extracellular vesicles (EVs) as key mediators of intercellular communication, carrying a complex cargo that includes extracellular matrix (ECM) components and associated modulators. Among them, ADAMTS proteases are emerging as pivotal regulators due to their ability to orchestrate precise ECM remodeling events and influence cellular behavior in pathological contexts such as cancer, vascular diseases, and tissue regeneration. Notably, the identification of specific ADAMTS family members within EV populations suggests that EVs may serve as vehicles for paracrine delivery and localized proteolytic activity, enabling spatially and temporally restricted ECM modulation. This review synthesizes current knowledge on the association between EVs and ADAMTS proteases, including their known substrates, and highlights their converging roles in shaping the extracellular landscape. We also discuss key knowledge gaps, especially concerning the diversity of ADAMTS-EV interactions, their functional impact in different physiological and pathological settings, and some reflections regarding their potential translational opportunities.