In my talk I will show how studying the adaptation of cells to sphingolipid depletion using high-throughput genetics and systematic lipidomics has revealed a network of co-regulated lipids that modulates the secretion of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). Since sphingolipids have been substituted by ether lipids during evolution to be used as the lipid anchor in this type of proteins I will also be giving an evolutionary perspective.