USP5 (Isopeptidease T) cleaves linear and branched polyubiquitin (polyUb) with a preference for branched polymers (Wilkonson et al. 1995). It is Involved in the disassembly of unattached lysine-48-linked (K48) polyUb. It also binds linear and K63-linked polyUb with a lower affinity (Dayal et al. 2009).
thiol-dependent deubiquitinase activity of USP5:PolyUb [cytosol]