Ceramide synthases are central enzymes of the sphingolipid pathway and are important for the production of sphingolipids of different chain length. Sphingolipids of different chain length impact the physicochemical properties of membranes. Here we investigated by complexome profiling how the expression level of membrane proteins is affected in human colon cancer cells (Caco-2 and HCT-116) that were transduced with a shRNA against CerS4 or CerS5 to downregulate both enzymes.