– Gastrokine 1 (GKN1) belongs to the BRICHOS domain family and plays a major role in maintaining gastric mucosa integrity. GKN1 is highly expressed in gastric tissue and is secreted into the stomach but is not expressed in gastric cancer. GKN1-mediated inhibition of APP processing might represent a new approach for the prevention and therapy of Alzheimer’s disease (AD). In the presence of GKN2, GKN1 loses its ability to decrease cell proliferation, induce apoptosis, and inhibit epigenetic alterations in gastric cancer cells, that GKN2 may contribute to the homeostasis of gastric epithelial cells by inhibiting GKN1 activity. The loss of GKN1 function contributes to malignant transformation and proliferation of gastric epithelial cells in gastric carcinogenesis.