The glutathione-conjugate transporter protein DNP-SG ATPase was demonstrated to be identical to the independently cloned Ral-effector, Ralbp1. Glutathione-conjugate transport is linked to substrate-stimulated ATPase activity, while GTPase stimulating activity (GAP-activity), and clathrin-coated pit-binding activity was demonstrated for this protein by different groups of investigators. The relationship between these activities and physiological functions of Ralbp1 were not clear. The present studies were designed to address the hypothesis that the ability of Ralbp1 to couple the hydrolysis of ATP with the movement of substances, i.e. its transport activity, is the crucial element that allows Ralbp1 to function as a stress-defense protein. Results of these studies, demonstrating (1) the requirement of Ralbp1 for PKCα mediated resistance-signaling, (2) the identification of transmembrane spanning domains of Ralbp1 and requirement of membrane anchorage for transport function, and (3) the requirement of transport function for clathrin-dependent ligand-receptor endocytosis to occur, offer strong evidence in support of this proposal.