HOPs (homotypic fusion and protein sorting) complex serves as a tethering complex with GEF (guanine nucleotide exchange factor) activity for Rab7 to regulate early-to-late endosomal transition and late endosomal membrane maturation.While the role of HOPs is well established in yeast cells,the functional and mechanistic aspects in mammalian cells are yet to be defined.In this study, we report that RILP, a downstream effector of Rab7 that is not present in yeast, interacts with HOPs complex and recruits HOPs subunits to the late endosomal compartment.Structurally, the amino-terminal portion of RILP interacts with HOPs complex.Unexpected, this interaction is independent of Rab7.VPS41 subunit of HOPs complex was defined to be the major partner for interacting with RILP.The carboxyl-terminal region of VPS41 was mapped to be responsible for the interaction.Consistently, depletion of VPS41 by shRNA significantly retarded EGF-induced degradation of EGFR.In view of previous known role of RILP in EGFR endocytic trafficking, these results suggest that interaction of RILP with HOPs complex via VPS41 plays a role in endocytic trafficking of EGFR.