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We found that copper preloading reduces CDDP cytotoxicity, supporting a shared uptake mechanism for copper and cisplatin. CDDP\u2010induced CTR1 endocytosis requires both the amino\u2010terminal His\u2010Met motifs and the conserved 150MXXM154 pore\u2010motif, similar to copper\u2010mediated transport. Following internalization, CTR1 is routed through VPS35\u2010positive endosomes and ultimately targeted to lysosomes. However, unlike copper, CDDP suppresses local recycling of CTR1 to plasma membrane and delays its lysosomal delivery. While copper promotes rapid lysosomal clearance of CTR1, CDDP results in prolonged intracellular trafficking. Additionally, CDDP enhances lysosomal size and cathepsin activity, indicating lysosomal activation. 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