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Loss of <jats:italic>CMAH<\/jats:italic> has occurred independently in some other lineages, but is functionally intact in Old World primates, including our closest relatives, the chimpanzee. Although the biophysical and biochemical ramifications of losing tens of millions of Neu5Gc hydroxy groups at most cell surfaces remains poorly understood, we do know that there are multiscale effects functionally relevant to both sides of the host\u2013pathogen interface. Hominin <jats:italic>CMAH<\/jats:italic> loss might also contribute to understanding human evolution, at the time when our ancestors were starting to use stone tools, increasing their consumption of meat, and possibly hunting. Comparisons with chimpanzees within ethical and practical limitations have revealed some consequences of human <jats:italic>CMAH<\/jats:italic> loss, but more has been learned by using a mouse model with a human\u2010like <jats:italic>Cmah<\/jats:italic> inactivation. For example, such mice can develop antibodies against Neu5Gc that could affect inflammatory processes like cancer progression in the face of Neu5Gc metabolic incorporation from red meats, display a hyper\u2010reactive immune system, a human\u2010like tendency for delayed wound healing, late\u2010onset hearing loss, insulin resistance, susceptibility to muscular dystrophy pathologies, and increased sensitivity to multiple human\u2010adapted pathogens involving sialic acids. Further studies in such mice could provide a model for other human\u2010specific processes and pathologies involving sialic acid biology that have yet to be explored.<\/jats:p>","DOI":"10.1002\/cbic.201700077","type":"journal-article","created":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T14:42:29Z","timestamp":1492612949000},"page":"1155-1171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Biochemical, Cellular, Physiological, and Pathological Consequences of Human Loss of <i>N<\/i>\u2010Glycolylneuraminic Acid"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3705-9060","authenticated-orcid":false,"given":"Jonathan","family":"Okerblom","sequence":"first","affiliation":[{"name":"Biomedical Sciences Graduate Program University of California in San Diego  9500 Gilman Drive La Jolla CA 92093-0687 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-975X","authenticated-orcid":false,"given":"Ajit","family":"Varki","sequence":"additional","affiliation":[{"name":"Glycobiology Research and Training Center GRTC) and Center for Academic Research and Training in Anthropogeny CARTA) Departments of Medicine and Cellular and Molecular Medicine University of California in San Diego  La Jolla CA 92093-0687 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,9]]},"reference":[{"key":"e_1_2_16_1_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005462"},{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cww086"},{"key":"e_1_2_16_3_1","first-page":"537","volume-title":"Bacterial and Viral Infections","author":"Nizet V.","year":"2009"},{"key":"e_1_2_16_4_1","unstructured":"\u00a0"},{"key":"e_1_2_16_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1040670104"},{"key":"e_1_2_16_6_2","first-page":"543","volume":"66","author":"Born G. 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