Who moves the sphinx? An overview of intracellular sphingolipid transport

Lipid bilayers function as boundaries that enclose their content from the surrounding media, and the composition of different membrane types is accurately and dynamically tailored so that they can perform their function. To achieve this balance, lipid biosynthetic machinery and lipid trafficking events are intertwined into an elegant network. In this review, we focus on the intracellular movement of sphingolipids mediated by sphingolipid transfer proteins. Additionally, we will focus on the best characterized and understood mammalian sphingolipid transfer proteins and provide an overview of how they are hypothesized to function. Some are already well understood, while others remain enigmatic. A few are actual lipid transfer proteins, moving lipids from membrane to membrane, while others may have more of a sensor role, possibly reacting to changes in the concentrations of their ligands. Considering the substrates available for cytosolic sphingolipid transfer proteins, one open question that is discussed is whether galactosylceramide is a target. Another question is the exact mechanics by which sphingolipid transfer proteins are targeted to different organelles, such as how four phosphate adapter protein-2, FAPP2 is targeted to the endoplasmic reticulum. The aim of this review is to discuss what is known within the field today and to provide a basic understanding of how these proteins may work.