The incidence and mortality of lung cancer continue to increase annually, making it the leading cause of cancer-related deaths in our country. A substantial proportion of cases are diagnosed at advanced stages, when surgical resection is no longer feasible, highlighting the urgent need for more effective therapeutic strategies, including chemotherapy, molecular targeted therapy, and immunotherapy. Tyrosine kinase inhibitors (EGFR-TKIs) that target the epidermal growth factor receptor (EGFR) have been introduced into clinical practice; however, their therapeutic efficacy is limited to tumors harboring activating EGFR mutations, and the inevitable emergence of acquired resistance remains a significant clinical challenge. Surfactant protein D (SP-D), a pulmonary collectin with high affinity for mannose, binds to oligomannose-type of N-glycans within the extracellular domain of EGFR [1]. This interaction suppresses lung cancer progression by inhibiting both wild-type and mutant EGFR through multiple mechanisms, including the inhibition of ligand binding, receptor dimerization, and autophosphorylation [2] (Fig. 98.1).