Lipid droplets (LDs) are a cellular organelle that is consisted of a neutral lipid core, monolayer phospholipid membrane and proteins. Accumulated studies present that LDs are involved in lipid synthesis, storage, transportation, modification and hydrolysis, as well as in protein storage and degradation. Therefore, LD research plays important roles in understanding of metabolic diseases and development of bioenergy. LD structure-like proteins differ from other membrane proteins in that 1) they are barely detected in other cellular structures with bilayer phospholipid membrane, 2) they do not have any sequence similarity among their membrane targeting domains. In mammals and Drosophila perilipin family proteins (PLINs) are the major LD structure-like proteins. PLINs are not found in other organisms. In a popular genetic model organism, C. elegans, LD structure-like proteins are identified as DHS-3 and MDT-28. In green algae the major one is MLDP, while in bacteria RHA1 and PD630 it is MLDS. Although these proteins are not similar in sequence, their ability to target to the LDs not in their own host cells but also in other organisms suggests that a conservative affinity to monolayer phospholipid membrane has been maintained through bacteria to humans.