{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC31A2, also known as copper transporter 2 (CTR2), is a member of the CTR family that, despite sharing significant sequence homology with CTR1, displays distinct biochemical and functional characteristics. Early studies showed that CTR2 forms oligomeric membrane complexes and is primarily localized to intracellular compartments such as late endosomes and lysosomes, although in some cell types it can also be detected at the plasma membrane. These findings indicate that CTR2 plays a role in facilitating the transfer of copper from intracellular reservoirs to the cytosol, particularly under conditions of elevated copper levels."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional analyses have further revealed that CTR2 contributes to cellular copper uptake by stimulating the accumulation of copper in the cytosol; however, its transport activity is of lower affinity compared to CTR1. In addition, alterations in CTR2 expression affect the cellular response to platinum-based chemotherapeutics, such as cisplatin and carboplatin, indicating that CTR2 not only modulates copper homeostasis but also influences drug sensitivity and resistance. Such dual functions underscore its importance in both trace metal regulation and in determining the efficacy of platinum-containing drugs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIntriguingly, the interplay between CTR2 and CTR1 is critical for maintaining overall copper balance. Evidence shows that the absence of CTR1 leads to marked proteasomal degradation of CTR2 via ubiquitination, highlighting a stabilizing role of CTR1 on CTR2 protein levels. Moreover, variations in CTR2 expression have been linked to clinical features in cancers—such as clear cell renal cell carcinoma—suggesting that CTR2 may modulate angiogenic processes and serve as a prognostic indicator, thereby expanding its functional relevance beyond copper metabolism alone."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Peter V E van den Berghe, Dineke E Folmer, Helga E M Malingré, et al. 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