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Currently, this incompletely understood mechanism in pancreatic diseases including pancreatitis and pancreatic cancer, largely limits therapeutic options for these disorders. Recent evidence indicates that S1P significantly contributes to pancreatic diseases by modulating inflammation, promoting pyroptosis in pancreatic acinar cells, regulating the activation of pancreatic stellate cells, and affecting organelle functions in pancreatic cancer cells. Nevertheless, no review has encapsulated these advancements. Thus, this review compiles information about the involvement of S1P signaling in exocrine pancreatic disorders, including acute pancreatitis, chronic pancreatitis, and pancreatic cancer, as well as prospective treatment strategies to target S1P signaling for these conditions. The insights presented here possess the potential to offer valuable guidance for the implementation of therapies targeting S1P signaling in various pancreatic diseases.<\/jats:p>","DOI":"10.3390\/ijms252111474","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T07:51:29Z","timestamp":1729842689000},"page":"11474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of Sphingosine-1-Phosphate Signaling Pathway in Pancreatic Diseases"],"prefix":"10.3390","volume":"25","author":[{"given":"Fei","family":"Fu","sequence":"first","affiliation":[{"name":"West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanmeng","family":"Li","sequence":"additional","affiliation":[{"name":"Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Wu","sequence":"additional","affiliation":[{"name":"Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Du","sequence":"additional","affiliation":[{"name":"West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-7236","authenticated-orcid":false,"given":"Chenxia","family":"Han","sequence":"additional","affiliation":[{"name":"West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cca.2020.10.013","article-title":"Iron metabolism and the exocrine pancreas","volume":"511","author":"Kimita","year":"2020","journal-title":"Clin. 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