Previous studies have suggested a role for cytosolic Ca2+-independent phospholipase A(2) (PLA(2)) activity in the formation of endosome membrane tubules that participate in the export of transferrin (Tf) and transferrin receptors (TfR) from sorting endosomes (SEs) and the endocytic recycling compartment (ERC). Here we show that the PLA(2) requirement is a general feature of endocytic trafficking. The reversible cytoplasmic PLA(2) antagonist ONO-RS-082 (ONO) produced a concentration-dependent, differential block in the endocytic recycling of both low-density lipoprotein receptor (LDLR) and TfRs, and in the degradative pathways of LDL and epidermal growth factor (EGF). These results are consistent with the model that a cytoplasmic PLA(2) plays a general role in the export of cargo from multiple endocytic compartments by mediating the formation of membrane tubules. (C) 2009 Elsevier Inc. All rights reserved.