UCHL1 and type 2 diabetes mellitus: Studies have also reported the downregulated proteasome activity, accumulation of polyubiquitinated proteins [27,50,73] and deficiency in the deubiquitinating enzyme UCHL1 (ubiquitin carboxyl-terminal esterase L1 [ubiquitin thiolesterase]) [73] in the T2DM donor islets, suggesting a dysfunctional ubiquitin/proteasome system (UPS) (Figure 3).