Palmitoylation as a Signal for Delivery.

The ligands and receptors in immune checkpoint signaling are typically transmembrane proteins, which may be regulated by palmitoylation as a reversible lipid modification. Our recent work demonstrated that palmitoylation reduces the lysosomal degradation of PD-L1 trafficking and may present a new therapeutic target. To facilitate future investigations on palmitoylation and immune checkpoints, here we summarize the molecular roles of palmitoylation on protein stability, trafficking, membrane association, and protein-protein interaction. The biological effects of palmitoylation are exemplified by well-studied substrates such as Ras, EGFR, and Wnt proteins. Finally, the strategies for targeting protein palmitoylation are discussed to facilitate future translational studies.