IL‐36R signaling has been implicated in various inflammatory diseases such as psoriasis and colitis by modulating the production of pro‐inflammatory cytokines and chemokines.[29, 30, 31] A phase I clinical trial with the IL‐36R antibody (Spesolimab) for generalized pustular psoriasis (GPP) has achieved promising outcomes and clinical trials for inflammatory bowel disease are on the way.[48] In this study, we have discovered a pro‐inflammation‐independent role of IL‐36R signaling in NSCLC development (Figure S7C, Supporting Information). The gene discussed is IL1RL2; the disease is colitis.