Ceramide-based lipids self-aggregate in cell membranes and form separate phases less fluid than the bulk phospholipids. These sphingolipid-based microdomains, or "lipid rafts" were originally proposed to sort membrane proteins along the cellular pathways of membrane transport. At present, most research focuses on the organizing function during signal transduction. Sphingolipids are synthesized in a pathway that begins in the ER and is completed in the Golgi apparatus, but these lipids are enriched in the plasma membrane and in endosomes, where they perform many of their functions. Transport occurs via vesicles and monomeric transport in the cytosol. Sphingolipids are virtually absent from mitochondria and the ER, but constitute a 20-35 molar fraction of plasma membrane lipids. In experimental animals, feeding sphingolipids inhibits colon carcinogenesis, reduces LDL cholesterol and elevates HDL cholesterol. Other sphingolipids Sphingolipids are universal in eukaryotes but are rare in bacteria and archaea. Bacteria that do produce sphingolipids are found in family Sphingomonadaceae, some members of the FCB group, some members of the Bdellovibrionota, and some members of the Myxococcota. Yeast sphingolipids Because of the incredible complexity of mammalian systems, yeast are often used as a model organism for working out new pathways. These single-celled organisms are often more genetically tractable than mammalian cells, and strain libraries are available to supply strains harboring almost any non-lethal open reading frame single deletion. The two most commonly used yeasts are Saccharomyces cerevisiae and Schizosaccharomyces pombe, although research is also done in the pathogenic yeast Candida albicans. In addition to the important structural functions of complex sphingolipids (inositol phosphorylceramide and its mannosylated derivatives), the sphingoid bases phytosphingosine and dihydrosphingosine (sphinganine) play vital signaling roles in S. cerevisiae. These effects include regulation of endocytosis, ubiquitin-dependent proteolysis (and, thus, regulation of nutrient uptake ), cytoskeletal dynamics, the cell cycle, translation, posttranslational protein modification, and the heat stress response. Additionally, modulation of sphingolipid metabolism by phosphatidylinositol (4,5)-bisphosphate signaling via Slm1p and Slm2p and calcineurin has recently been described. Additionally, a substrate-level interaction has been shown between complex sphingolipid synthesis and cycling of phosphatidylinositol 4-phosphate by the phosphatidylinositol kinase Stt4p and the lipid phosphatase Sac1p. Plant sphingolipids Higher plants contain a wider variety of sphingolipids than animals and fungi. Disorders There are several disorders of sphingolipid metabolism, known as sphingolipidoses. The main members of this group are Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease and Metachromatic leukodystrophy. They are generally inherited in an autosomal