MUC6, a mucin-encoding gene, is mainly expressed in the gastric epithelium and duodenal Brunner's glands. The encoded MUC6 protein, as a key component of gastric gland mucus, plays a crucial role in maintaining gastric mucosal integrity. It interacts with TFF2, a peptide in the trefoil factor family, via non-covalent lectin interactions and potentially disulfide bridges, which stabilizes the gastric mucus barrier [2].

Genetic variants in MUC6 have been associated with multiple diseases. MUC6 VNTR repeat expansion is linked to Alzheimer's disease pathologic severity, especially tau proteinopathy, and may influence AP2A2 gene expression [1]. In cancer research, decreased MUC6 expression is seen in invasive cancers of the stomach, pancreas, and bile duct. In lung invasive mucinous adenocarcinoma, MUC6 expression is a preferable prognostic biomarker, with MUC6-expressing cells showing lower proliferation, motility, and invasiveness [3]. In gastric cancer, promoter methylation of MUC6 leads to its down-regulation and promotes cancer progression [4]. Polymorphisms in MUC6 may also be related to the risk of Helicobacter pylori infection and gastric cancer, as well as the susceptibility to and clinicopathological characteristics of hepatocellular carcinoma [6,7]. Genome-wide association studies have identified the MUC6 locus as being associated with peptic ulcer disease [5].

In conclusion, MUC6 is essential for maintaining the integrity of the gastric mucus barrier. Research on MUC6, especially through genetic association studies, has revealed its significance in multiple disease areas such as Alzheimer's disease, various cancers, and peptic ulcer disease. These findings contribute to a better understanding of disease mechanisms and may potentially lead to new diagnostic and therapeutic strategies.