STK11 (also known as LKB1) encodes a serine/threonine kinase that functions as a tumor suppressor with critical roles in cellular metabolism, growth control, and immune regulation. The protein acts as a negative regulator of mTORC1 signaling and plays essential roles in establishing cell polarity, regulating cell proliferation, and mediating DNA damage responses 1. STK11 is frequently mutated in lung adenocarcinoma, where loss-of-function mutations, particularly when co-occurring with KEAP1 mutations, promote ferroptosis resistance and create dependencies on metabolic enzymes like SCD1 2. STK11 mutations are strongly associated with immunotherapy resistance in NSCLC, especially in KRAS-mutant tumors, by creating an immunosuppressive tumor microenvironment characterized by reduced immune cell infiltration and altered gene expression profiles 3. Both mutations and deletions of STK11 correlate with worse outcomes to immune checkpoint inhibitors and chemoimmunotherapy, with deletions showing comparable clinical impact to mutations 4. Germline STK11 mutations cause Peutz-Jeghers syndrome and are associated with a novel STK11 adnexal tumor characterized by complete loss of STK11 protein expression 56. Therapeutic restoration of STK11 function can reactivate autophagy and reverse immunosuppression, potentially overcoming resistance to anti-PD-1 therapy 7.