The released TIMP3, containing a residual leucine at its N-terminal, could inhibit ADAM17 and ADAMTS4 but not MMPs, although in synovial fluid from patients with osteoarthritis, there was sufficient MMP activity to cleave LAP-TIMP3 and release active TIMP3 (Alberts et al., 2019), suggesting that LAP-TIMP3 may be useful for anti-inflammatory therapy. Here, ADAMTS4 is linked to osteoarthritis.