Abstract: In recent years, sphingolipids have garnered increasing attention for their roles in modulating intracellular signaling events. Circulating factors associated with obesity promote excess accumulation of ceramide or glucosylceramide derivatives, which impair insulin action in peripheral tissues. In this issue, Villa et al. (2009) provide evidence that, in yeast, the PAQR superfamily of receptors mediate their effects via a novel ceramidase activity, generating sphingoid base as a second messenger.