CLDN23 (claudin-23) is a tight junction protein that mediates calcium-independent cell-cell adhesion through obliteration of intercellular space 1. As a four-transmembrane claudin family member located on chromosome 8.1, CLDN23 plays a structural role in maintaining the intestinal epithelial barrier 2. Mechanistically, CLDN23 expression is regulated by the microbial metabolite n-butyrate via SP1 and AMPK signaling pathways, which enhances intestinal barrier integrity 2. The gene is transcriptionally suppressed in colorectal cancer through an ELF4/ITGB8-AS1/EZH2-mediated histone H3K27me3 modification pathway that promotes cancer cell proliferation and invasion 3. CLDN23 is frequently downregulated in intestinal-type gastric cancer, implicating it as a candidate tumor suppressor gene 14. Beyond gastric malignancy, reduced CLDN23 expression is associated with colorectal cancer progression and poorer prognosis 56. Additionally, CLDN23 shows altered DNA methylation in childhood allergy disorders, suggesting involvement in barrier-related immune dysfunction 7, and genetic variants in CLDN23 are linked to irritable bowel syndrome susceptibility with pleiotropic effects on cardiovascular traits 8. These findings identify CLDN23 as both a critical intestinal barrier component and a tumor suppressor gene with potential as a prognostic biomarker and therapeutic target.