The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists

Sphingolipids and glycosphingolipids are among the most structurally diverse and complex compounds in the mammalian metabolome. They are well known to play important roles in biological architecture, cell-cell communication, and cellular regulation, and for many biological processes, multiple sphingolipids are involved. Thus, it is not surprising that untargeted genetic/transcriptomic/pharmacologic/metabolomic screens have uncovered changes in sphingolipids and sphingolipid genes/proteins while studying physiological and pathological processes. Consequently, with increasing frequency, both targeted and untargeted mass spectrometry methodologies are being used to conduct sphingolipidomic analyses. Interpretation of such large data sets and design of follow-up experiments can be daunting for investigators with limited expertise with sphingolipids (and sometimes even for someone well-versed in sphingolipidology). Therefore, this review gives an overview of essential elements of sphingolipid structure and analysis, metabolism, functions, and roles in disease and discusses some of the items to consider when interpreting lipidomics data and designing follow-up investigations.