Ceramide is central to sphingolipid metabolism and can be generated de novo (blue), through hydrolysis of complex sphingolipids (yellow) or via the salvage pathway (red). In the de novo pathway, serine palmitoyltransferase (SPT) catalyzes the first reaction resulting in 3-ketosphinganine, which is reduced to dihydrosphingosine (dhSph), further metabolized to dihydroceramide (dhCer) by ceramide synthases (CerSs), and desaturated by dihydroceramide desaturase (DES) to generate ceramide. Ceramide is used as a building block for complex sphingolipids such as sphingomyelin, glycosphingolipids, and gangliosides. These complex sphingolipids can be hydrolyzed to regenerate ceramide. Ceramide is hydrolyzed by ceramidases (CD) to generate sphingosine, which serves as substrates for CerSs or SK1 to regenerate ceramide via the salvage pathway or to generate sphingosine 1-phosphate (S1P). Further hydrolysis of S1P by S1P lyase represents the exit from sphingolipid metabolism. This schematic is focused on the enzymes discussed in the text and does not include all enzymes involved in sphingolipid metabolism.