USP15 deubiquitinates and interacts with the extracellular-signal-regulated kinase 2 (ERK2), but it does not regulate the stability of ERK2, resulting in an increase in the pERK1/2 levels to further enhance the TGFβ/SMAD2 signaling pathway and suppress osteoarthritis progression. The gene discussed is MAPK1; the disease is osteoarthritis.