Ceramide phosphoethanolamine (CPE) is the major sphingolipid in invertebrates and in some bacterial species. It has been also detected in mammalian cells, although only in trace amounts. Complete understanding of the biophysical and physiological relevance of CPE is still lacking, and its biological role is still an open question. CPE differs in its biosynthetic mechanisms from sphingomyelin, due to the specific CPE synthase in invertebrates. In contrast to well-established sphingomyelin/cholesterol interactions that result in the formation of ordered membrane domains, the formation of ordered CPE/cholesterol domains is not favored. CPE might be crucial for the early development of Drosophila melanogaster, and it might be involved in the developmental stages of Trypanosoma brucei. As a Bacteroidetes-associated sphingolipid, CPE might also be involved in maintenance of these bacteria in their ecological niches. Therefore, efficient detection of CPE in biological systems is needed to better define its distribution and biological role(s). Display omitted •Ceramide phosphoethanolamine (CPE) is the major sphingolipid in invertebrates.•CPE and dihydroCPE are one of the most dominant sphingolipids in Bacteroidetes.•CPE differs in its biosynthetic mechanisms from sphingomyelin.•The formation of ordered CPE/cholesterol domains is not favored.•CPE might be crucial for the development of some insects and protozoa.