T cell–mediated immunity relies on the presentation of diverse antigens that enable immune surveillance against infections. While classical MHC molecules present peptide antigens, the CD1 family extends this system to lipid antigens, allowing T cells to recognize both antigen lipids and self-derived lipids. Among the five human CD1 isoforms, CD1a–d present lipid antigens at the cell surface, whereas CD1e mainly functions as an intracellular lipid transfer protein localized within the endosomal and lysosomal compartments of dendritic cells. Through this function, CD1e can indirectly regulate T cell responses by influencing the repertoire of lipid antigens available for other CD1-lipid presentations. However, the precise mechanism by which CD1e binds and transfers lipids remains poorly understood. In this study, we performed lipidomic analyses and found that CD1e, similar to other CD1 isoforms, associates with a range of endogenous lipids, such as Phosphatidylcholine (PC) and Sphingomyelin (SM) species. We also successfully loaded target lipids onto recombinant CD1e in vitro and analyzed using isoelectric focusing experiment. These support CD1e’s role as an active lipid-binding protein. To further investigate the molecular basis of lipid binding and transfer by CD1e, we initiated structural studies and setting crystallization trials and obtained promising preliminary conditions for mechanistic study. In terms of the mechanism that CD1e transferring lipids, we identified for the first time a direct interaction between CD1e and CD1c. Interestingly, by characterizing surface plasmon resonance (SPR) experiment, we found that the binding between CD1e and CD1c is pH dependent, showing stronger interaction under acidic conditions, which is consistent with the lysosomal environment where CD1e normally functions. The direct interaction that observed between CD1e and other CD1 molecules may represent a new regulatory mechanism that controls lipid transfer and shapes the repertoire of antigens presented to T cells. Understanding this mechanism expands the role of the CD1 family and might provide new insights into how CD1e contributes to the coordination of lipid processing and CD1-restricted T cell signaling, deepening our understanding of how lipid antigen presentation integrates into the broader network of human immune regulation.