UBE2N, a ubiquitin-conjugating enzyme E2; STIP1, an E3 ubiquitin ligase; and UBE2L3, also a ubiquitin ligase, are all key players in the ubiquitin pathway and critical for misfolded protein degradation [41]; our results suggest that, in T2D, hypoglycemia may be predisposed to increased protein misfolding, therefore activating this pathway. This evidence concerns the gene UBE2L3 and type 2 diabetes mellitus.