GKN2 (gastrokine 2) is a tumor suppressor gene with primary expression in the gastric epithelium and trophoblastic tissues, functioning as a regulator of cell proliferation and differentiation. 1 GKN2 exhibits gestational age-dependent and compartment-specific expression patterns in placental tissues, with particular localization in extravillous trophoblasts and myofibroblasts, suggesting roles in placental development and physiology. 1 Mechanistically, GKN2 inhibits gastric cancer cell proliferation, migration, and invasion through inactivation of the JAK2/STAT3 pathway. 2 The protein forms a functional heterodimer with TFF1, producing synergistic antiproliferative and pro-apoptotic effects in gastric cancer cells via G1/S cell cycle arrest and caspase-3/7 activation. 3 GKN2 expression is significantly downregulated in gastric and non-small cell lung cancers compared to normal tissues, with reduced expression correlating with larger tumor size and P53 mutations. 4 Promoter methylation by DNMT3B contributes to GKN2 silencing in lung cancer. 4 Clinically, GKN2 serves as a potential non-invasive serum biomarker for early gastric cancer diagnosis, with particularly high discriminatory value (AUC 0.822) between benign gastric disease and early gastric cancer. 5 GKN2 expression shows sexual dimorphism, with 7.2-fold higher expression in men than women, potentially explaining differential gastric cancer susceptibility between sexes. 6