Structure and function of mammalian sphingolipids in health and disease

Sphingolipids are a major lipid class in vertebrates with a high structural and functional diversity. As part of the cellular membrane bilayers, they are of major importance for the compartmentalization of the cellular space. Sphingolipids facilitate the formation of membrane-protein networks by providing membrane platforms, they modulate signaling processes, and affect cell–cell interactions. Soluble sphingolipid derivatives like sphingosine-1-phosphates are important direct mediators of cellular signaling processes. Many cellular and physiological processes are associated with sphingolipids including cellular growth, differentiation, apoptosis, cell–cell interactions, inflammation, and chemotaxis (see, for example, [Hannun and Obeid, 2002, Maceyka and Spiegel, 2014]). In addition, sphingolipids are important components of organized tissues and (extra)cellular structures like the lipid skin barrier or the myelin sheaths. The occurrence and distribution of specific sphingolipids is tissue- and cell type-dependent and can vary across different states of differentiation, activation, or transformation. This implies an adjustment of cellular sphingolipid metabolism based on expression, turnover, and activity of specific enzyme sets. Genetic disorders of sphingolipid anabolism and catabolism affect certain cell types and structures more than others and lead to clinically heterogeneous pathologies. However, defects in genes affecting the same physiological process often give rise to similar pathologies.