Proteins from the NLP family (Nep1-like proteins) are found in a variety of taxonomically unrelated microorganisms (fungi, oomycetes, bacteria). Such microorganisms are widespread and can infect different crop plants, especially dicotyledons such as potatoe, tomatoe, soybean, tobacco and hop. Some NLP proteins are cytotoxic to dicotyledonous plants, and cause tissue necrosis and induce immune response of the plant. In addition to cytotoxic proteins, there are also NLP proteins that are not cytotoxic. NLP proteins are structurally similar to actinoporins, toxins that form pores into the cell membrane. NLP proteins bind to sphingolipids, just like actinoporins. The yeast Saccharomyces cerevisiae, which is a simple and well-known model organism and contains sphingolipids that are similar to plant sphingolipids, has been selected for the study of the interaction between NLP proteins and sphingolipids. We found that the cytotoxic protein NLPPya binds to the yeast protoplasts more strongly and is also more toxic to yeasts than the protein HaNLP3, which is not cytotoxic to plants. To examine the binding of NLP proteins to yeast sphingolipids we used two mutants with impaired sphingolipid mannosylation, and compared them to the wild type cells. We found that most proteins bind to the BY4742 csg2Δ strain which does not have manosylated sphingolipids, but has an increased amount of ceramides and inositol-phosphoryl ceramides.