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GSLs cluster to form membrane microdomains (lipid rafts) on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL\u2010mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17) is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Src family tyrosine kinase Lyn and the G<jats:italic>\u03b1<\/jats:italic>i subunit of heterotrimeric G proteins. The very long fatty acids C24:0 and C24:1 are the main ceramide components of LacCer in neutrophil plasma membranes and are directly connected with the fatty acids of Lyn and G<jats:italic>\u03b1<\/jats:italic>i. These observations suggest that the very long fatty acid chains of ceramide are critical for GSL\u2010mediated outside\u2010in signaling. 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