ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5)

ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) is a secreted zinc-dependent metalloendopeptidase belonging to the ADAMTS family. It contains multiple protein modules including a propeptide region, catalytic domain, disintegrin-like domain, cysteine-rich region, spacer domain, and two C-terminal thrombospondin motifs. Its primary biological function is cleaving aggrecan—a major structural proteoglycan—in articular cartilage. Overactivity of ADAMTS5 leads to excessive aggrecan degradation implicated in joint diseases such as osteoarthritis. Genetic knockout studies confirm its central role as an “aggrecanase” responsible for pathological cartilage loss; thus it has become an important therapeutic target for disease-modifying interventions aimed at slowing or preventing joint degeneration. However, because it also participates in normal connective tissue maintenance throughout development and adulthood—including roles outside joints—therapeutic strategies must balance efficacy against potential systemic side effects from broad inhibition.

Other names

ADAMTS11Aggrecanase-2ADMP-2A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 5 (aggrecanase-2)A disintegrin and metalloproteinase with thrombospondin motifs 11ADAM-TS 11

Inhibition of aggrecan-degrading activity to prevent cartilage breakdown; Monoclonal antibodies or small molecules that block the catalytic or ancillary domains to reduce enzyme function; Endogenous inhibition by TIMP3 binding to the active site