Ca2+-independent phospholipase A2(iPLA2) is a subclass of enzyme that catalyzes the release of fatty acids from phospholipids.Previous findinginour lab showedthat iPLA2activity is required for microglia chemotaxis and that inhibition ofiPLA2causes a trafficking defect of c-Src, remainingin the endosomal recycling compartment. This suggests the requirement ofiPLA2activity for vesicular recycling.Rab proteins, a group of small GTPases, regulate intracellular trafficking and maintain organellar identity by controlling budding, transport, tethering, docking, and fusion of recycling vesicles.Thus, one might imagine a possibility of the regulation ofiPLA2by Rab proteins.In this study, we investigated the interaction betweeniPLA2and Rab proteins usingGST pull down assaysand found Rab5 is specifically binding toiPLA2.Using recombinantHis-tag ankyrinrepeats (HisANK)protein, we confirmedthat Rab5 is binding to ankyrin repeats ofiPLA2. We alsoanalyzedthe effect of ATPbinding to the nucleotide-binding domain ofiPLA2on theinteractionwith Rab5 and demonstrated that ATP binding toiPLA2inhibits the interaction withRab5. Microscopicobservations showed thatADP stimulation of microglia inducesco-localization ofiPLA2and Rab5 in vesicular compartmentsaound nucleusinstarved microgliacells.Furthermore, expression of constitutively active Rab5 (Rab5CA) facilitates the association ofiPLA2 with vesicles.These results suggest that Rab5 interacts withiPLA2andregulates the activity or localizationforiPLA2.