Given that RPS27L knockdown destabilizes FANCD2 and FANCI via p62-mediated autophagy-lysosome pathway, leading to impaired ICL repair and sensitization of lung cancer cells to MMC, our study, therefore, suggests that RPS27L might serve as an attractive target for the sensitization of ICL-inducing chemotherapy. The gene discussed is FANCD2; the disease is lung carcinoma.