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Being among the most dynamic cells of the digestive system, EGCs react to cues in their surrounding microenvironment and communicate with various cell types and systems within the gut. Morphological studies and recent single cell RNA sequencing studies have unveiled heterogeneity among EGC populations with implications for regional functions and roles in diseases. In gastrointestinal disorders, including inflammatory bowel disease (IBD), infections and cancer, EGCs modulate neuroplasticity, immune responses and tumorigenesis. Recent evidence suggests that EGCs respond plastically to the microenvironmental cues, adapting their phenotype and functions in disease states and taking on a crucial role. They exhibit molecular abnormalities and alter communication with other intestinal cell types, underscoring their therapeutic potential as targets. This review delves into the multifaceted roles of EGCs, particularly emphasizing their interactions with various cell types in the gut and their significant contributions to gastrointestinal disorders. Understanding the complex roles of EGCs in gastrointestinal physiology and pathology will be crucial for the development of novel therapeutic strategies for gastrointestinal disorders.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1408744","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T01:23:15Z","timestamp":1718673795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["From diversity to disease: unravelling the role of enteric glial cells"],"prefix":"10.3389","volume":"15","author":[{"given":"Sneha","family":"Santhosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Zanoletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lincon A.","family":"Stamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene M.","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Matteoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.32","article-title":"The enteric nervous system and neurogastroenterology","volume":"9","author":"Furness","year":"2012","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"dev.182543","DOI":"10.1242\/dev.182543","article-title":"Gut innervation and enteric nervous system development: a spatial, temporal and molecular tour de force","volume":"148","author":"Kang","year":"2021","journal-title":"Development"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0271-2","article-title":"Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility","volume":"17","author":"Spencer","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2022","article-title":"The enteric nervous system","volume":"103","author":"Sharkey","year":"2023","journal-title":"Physiol Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00423-7","article-title":"Enteric glial biology, intercellular signalling and roles in gastrointestinal disease","volume":"18","author":"Seguella","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e14440","DOI":"10.1111\/nmo.14440","article-title":"How big is the little brain in the gut? 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