USP14 and neurodegenerative disease: In agreement with this, a highly selective inhibitor of USP14, IU1, (Figure 2B) (IC50 of Ub-AMC hydrolysis by proteasome-bound USP14 is 4.7 ± 0.7 μM), enhanced the destruction of several important proteasome substrates (Tau, TDP-43) involved in the development of neurodegenerative diseases [59].