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Appendicitis is one of the most common indications for emergency abdominal surgery, costing healthcare systems billions of dollars globally and causing tens of thousands of deaths annually. Yet, recent studies have indicated that the appendix may serve important protective functions in fortifying the body's immune response against invading pathogens and re\u2010inoculating the gut with commensal bacteria after periods of gastrointestinal illness. While the cecal appendix was once believed to be a synapomorphy of hominoids (humans and other great apes), recent studies suggested that it is a recurrent trait found in several other species of primates, rodents, lagomorphs, marsupials, and monotremes. Mapping appendiceal and other gastrointestinal traits across a mammalian consensus phylogeny revealed that the cecal appendix has evolved independently numerous times throughout mammalian evolution, significantly more than would be expected due to chance alone, suggesting that the appendix is adaptively advantageous. However, attempts to identify an overarching ecological, behavioral, dietary, or environmental factor driving some species to evolve an appendix have been largely unsuccessful, indicating that the cecal appendix has a complex and diverse evolutionary history. This review discusses the current understanding of the pathophysiology, evolution, and possible functions of the appendix, both within humans and broadly across the class Mammalia.<\/jats:p>","DOI":"10.1002\/ar.24917","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T09:32:02Z","timestamp":1648805522000},"page":"972-982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A review of the function and evolution of the cecal appendix"],"prefix":"10.1002","volume":"306","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3738-0903","authenticated-orcid":false,"given":"Heather F.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Anatomy Midwestern University  Glendale Arizona USA"},{"name":"School of Human Evolution and Social Change Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00276-007-0182-8"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.280.5.G922"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00264817"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.290.6475.1125"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/338371a0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.296.6627.953"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.296.6627.956"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ca.22269"},{"key":"e_1_2_7_10_1","first-page":"83","article-title":"The true caecal apex, or the vermiform appendix: Its minute and comparative anatomy","volume":"35","author":"Berry R. 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