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CMTM4, a subunit of the IL\u201017 receptor (IL\u201017R), has been implicated in immune responses, but its role in GC development remains unclear. In this study, we investigate the role of CMTM4 during <jats:italic>H. pylori<\/jats:italic>\u2010induced gastric carcinogenesis using <jats:italic>Cmtm4<\/jats:italic> knockout (KO) mice. Our findings indicated that <jats:italic>Cmtm4<\/jats:italic> deficiency inhibited GC development and pseudopyloric metaplasia, while reducing DNA damage in the gastric mucosa. Mechanistically, <jats:italic>Cmtm4<\/jats:italic> deletion downregulated the IL\u201017 signaling pathway in GC. Specifically, it suppressed the expression of IL\u201017 receptor RC (IL\u201017RC) and its downstream signaling molecules, resulting in the inhibition of nuclear factor\u2010\u03ba B (NF\u2010\u03baB) activation and a decrease in NADPH oxidase\u20101 (NOX1) levels. These results suggest that <jats:italic>Cmtm4<\/jats:italic> deletion suppresses <jats:italic>H. pylori<\/jats:italic>\u2010induced gastric carcinogenesis and precancerous lesion formation, potentially through the regulation of IL\u201017RC\/NF\u2010\u03baB\/NOX1 signaling, which may represent a new target for the early prevention of GC.<\/jats:p>","DOI":"10.1111\/pin.70020","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T06:20:43Z","timestamp":1748413243000},"page":"278-290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>Cmtm4<\/i> Deficiency Inhibits <i>Helicobacter pylori<\/i>\u2010Induced Gastric Carcinogenesis"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1727-8642","authenticated-orcid":false,"given":"Yanfei","family":"Lang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Peking University Third 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