In the March 2023 issue of Science Immunology, researchers working at the City of Hope National Medical Center reported on the discovery the mechanisms by which the spliced X-box–binding protein 1 (XBP1s) served essential functions in the IL-15-dependent survival of natural killer (NK) cells. Since XBP1s is known to play critical roles in MHCII expression, the unfolded protein stress response, and ultimately tumorigenesis, the study provided deep insights into the understanding of NK cell biology with translational potential.