CIDE domain containing proteins are involved in apoptosis and lipid metabolism, and four CIDE containing proteins, Drep1, Drep2, Drep3, and Drep4, have been identified in fly. In this study, we found that Drep3 interacts with Drep4 via the CIDE domain specifically, which completes the interaction map of Drep system in fly, cyclic interactions: Drep1âDrep2âDrep3âDrep4âDrep1. In addition, we analyzed the dynamic stoichiometry changes of Drep proteins upon binding to their binding partners. Our current studies will help us to understand Drep system in fly as well as CIDE domain for proteinâprotein interactions.