GKN1 (gastrokine 1) is a secreted protein primarily expressed in gastric mucosal pit cells that functions as a tumor suppressor and maintains gastric epithelial homeostasis 1. Primary function involves inhibiting gastrin-induced cell proliferation through downregulation of the gastrin-CCKBR signaling pathway and suppression of NF-κB and β-catenin signaling 2. Mechanistically, GKN1 exhibits anti-amyloidogenic properties by interacting with amyloid precursor protein (APP) and inhibiting Aβ production, while also regulating autophagy-mediated protein degradation 34. GKN1 expression is significantly downregulated in H. pylori-infected gastric mucosa and is absent in gastric cancer, suggesting its role as a protective factor 15. During chr2 atrophic gastritis, IL-33 promotes GKN1 degradation through the AMPK-ULK1 autophagy axis, contributing to disease progression 4. Beyond gastric pathology, GKN1 regulates metabolic homeostasis and obesity susceptibility through microbiome modulation 6, and higher placental GKN1 expression is associated with impaired pancreatic beta cell function in gestational diabetes 7. Combined serum measurement of IL-33 and GKN1 shows diagnostic potential for gastric pathology monitoring 4.