Although targeting the surface distribution of PD-L1 by modulating N-glycan branching is emerging as an exciting approach to boost the immune system against cancer cells [50, 83–85], the clinical development of currently existing inhibitors that impact processing or “trimming” of the glucosylated, high-mannose side chains by inhibiting one or more of the specific processing glycosidases/mannosidases, is still lacking regarding effective modifications capable of improving their therapeutic efficacy, selectivity, potency, and tolerability. The gene discussed is CD274; the disease is cancer.