A mutant TIMP-3 (Tissue Inhibitor of MetalloProteinase-3) polypeptide wherein an additional residue or residues, for example an alanine residue, precedes the N-terminal residue of the TIMP-3 polypeptide; or wherein the residue corresponding to Threonine2 of TIMP-3 is mutated to Glycine. Such a mutant is considered to retain activity as an inhibitor of ADAMs, such as TACE, ADAMTS-4 and ADAMTS-5, but to have reduced activity as an inhibitor of MMPs.