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I\u03b1I is a complex containing the proteoglycan bikunin to which heavy chain proteins are covalently attached to the chondroitin sulfate chain. Besides its matrix protective activity through protease inhibitory action, I\u03b1I family members interact with extracellular matrix molecules and most notably hyaluronan, inhibit complement, and provide cell regulatory functions. Recent evidence for the diverse roles of the I\u03b1I family in both biology and pathology is reviewed and gives insight into their pivotal roles in tissue homeostasis. 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