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Conventionally, antimicrobial peptides (AMPs) have been regarded as the dominant endogenous antimicrobial molecule; however, AMPs are not sufficient to account for the full spectrum of antimicrobial\u2010immunomodulatory duality occurring within the human body. The threat posed by pathogenic microbes is pervasive with the capacity for widespread impact across many organ systems and multiple biochemical pathways; accordingly, the host needs the capacity to react with an equally diverse response. This can be attained by having EAIMs that traverse the full range of molecular size (small to large molecules) and structural diversity (including molecules other than peptides). This review identifies multiple molecules (peptide\/protein, lipid, carbohydrate, nucleic acid, small organic molecule, and metallic cation) as EAIMs and discusses the possibility of cooperative, additive effects amongst the various EAIM classes during the host response to a microbial assault. This comprehensive consideration of the full molecular diversity of EAIMs enables the conclusion that EAIMs constitute a previously uncatalogued structurally diverse and collectively underappreciated immuno\u2010active group of integrated molecular responders within the innate immune system's first line of defence.<\/jats:p>","DOI":"10.1002\/cbic.202400089","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T22:03:13Z","timestamp":1713996193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Endogenous Antimicrobial\u2010Immunomodulatory Molecules: Networking Biomolecules of Innate Immunity"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2042-6220","authenticated-orcid":false,"given":"Donald F.","family":"Weaver","sequence":"first","affiliation":[{"name":"Departments of Chemistry and Medicine University of Toronto Krembil Research Institute 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