The UDP-glucoseceramide glycosyltransferase (UGCG) is a key enzyme in the sphingolipidmetabolism by generating the precursor for all glycosphingolipids (GSL), essentialfor proper cell function. But the UGCG is also overexpressed in several cancertypes and correlates with multidrugresistance protein 1 (MDR1) geneexpression. This enzyme is responsible for efflux of toxic substances andprotects cancer cells from cell damage through chemotherapeutic agents. Studiesshowed a connection between UGCG and MDR1overexpression and multidrug resistance development, but the precise mechanismsunderlying are unknown. Here, we give an overview about the UGCG and itsconnection to MDR1 in multidrugresistant cells. Furthermore, we focus on UGCG transcriptional regulation, theimpact of UGCG on cellular signaling pathways and the effect of UGCG and MDR1 on the lipid composition ofmembranes and how this could impact multidrug resistance development. To ourknowledge, this is the first review presenting an overview about UGCG withfocus on the relationship to MDR1 inthe process of multidrug resistance development.