Immunostasis is maintained by tolerance mechanisms like the programmed death-1 (PD-1) immune checkpoint. With the immunostasis, the immune system is able to defend against infections and cancer without causing autoimmune disorders. However, immune stimulation signals override the PD-1 immune checkpoint in autoimmune diseases, and the checkpoint is no longer able to sustain immunostasis. What drives Dr. Chen’s research is to improve therapies for autoimmune diseases by restoring immunostasis. Taking back control of the PD-1 immune checkpoint is one strategy to regain immunostastasis. To this end, multiple families of protein tools were engineered by leveraging the principles of immunology and protein engineering. In this seminar, discoveries and lessons that were learned from using these tools to modulate the PD-1 immune checkpoint will be presented and discussed.