Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been shown to positively regulate MHC I recycling and antigen cross-presentation to CD8 T cells, although it is unclear whether UCH-L1 directly deubiquitinates MHC I.46 Another DUB, USP14, facilitates MHC I-restricted direct antigen presentation, particularly the peptides derived from defective ribosomal products (DRiPs).47 These findings suggest that targeting E3 ubiquitin ligases and DUBs represents a potential strategy to modulate MHC expression and antigen presentation in vaccine development and other approaches of cancer immunotherapy. This evidence concerns the gene ZUP1 and cancer.