Lysosomes are thought to play a role in various aspects of heavy metal metabolism. In the present study we demonstrate for the first time the presence of a heavy metal ion transport protein in the lysosomal membrane. Uptake of radioactive silver both in highly purified lysosomal membrane vesicles and in purified intact lysosomes showed the typical kinetics of a carrier-mediated process. This transport was stimulated by ATP hydrolysis, and showed specificity for Ag + , Cu P+ , and Cd P+ . All biochemical properties of this lysosomal metal ion transporter could classify it as a heavy metal transporting P-type ATPase. Long Evans Cinnamon (LEC) rats, an animal model for the copper transport disorder Wilson disease, showed normal lysosomal silver transport.z 1998 Federation of European Biochemical Societies.