Gkn3, a member of the gastrokine family, is a secreted protein. Gastrokines are secreted by stomach mucus cells, and Gkn3 may play a role in mucosal protection systems in the proximal colon and duodenum, as its expression was noted in these regions along with other relevant genes [4]. It has also been associated with cell proliferation regulation and is potentially involved in the response to viral entry in neurons [2,3].

In mouse models, Gkn3 mRNA is a specific marker of mouse gastric corpus metaplasia (SPEM), undetectable in healthy gastric corpus but highly expressed in chronically inflamed stomachs, which helps in a more accurate assessment of SPEM [1]. Mouse Gkn3 expression is strongly up-regulated in (Tff2 -deficient) gastric atrophy, a pre -cancerous state, and Gkn3 overexpression inhibits proliferation in gastric epithelial cell lines [2]. In addition, early administration of dapagliflozin in db/db mice (a type 2 diabetes model) upregulated Gkn3 expression, which might be related to the preservation of pancreatic β -cell mass [5].

In conclusion, Gkn3 is involved in multiple biological processes. Its role in gastric metaplasia, gastric atrophy, and potentially in pancreatic β -cell mass preservation is revealed through mouse models. Understanding Gkn3 function contributes to the study of related disease mechanisms such as gastric pre -cancerous states and type 2 diabetes, providing potential insights for disease prevention and treatment.