ATPase copper transporting beta (ATP7B) (ATP7B)

ATPase copper transporting beta (ATP7B), also known as the Wilson disease protein, is a P-type ATPase primarily expressed in the liver that plays a central role in copper homeostasis [6, 11]. It functions by transporting copper from the cytosol into the trans-Golgi network for incorporation into ceruloplasmin and by facilitating the excretion of excess copper into the bile via vesicular trafficking [6, 15]. Mutations in the ATP7B gene lead to Wilson disease, a rare autosomal recessive disorder characterized by toxic copper accumulation in the liver, brain, and other tissues, resulting in hepatic cirrhosis and neuropsychiatric symptoms [5, 11]. In the context of oncology, ATP7B is a significant mediator of resistance to platinum-based chemotherapies, such as cisplatin and carboplatin, as it can sequester and efflux these agents from cancer cells [1, 3]. Current therapeutic interventions for Wilson disease include copper chelators like penicillamine and trientine, as well as zinc salts that block intestinal copper absorption [9, 10]. Emerging therapies include gene replacement strategies using adeno-associated virus (AAV) vectors to restore functional ATP7B expression in the liver [8]. Additionally, targeting ATP7B in cancer is being investigated as a strategy to overcome drug resistance and improve the efficacy of platinum-based treatments [1, 2].

Other names

Copper-transporting ATPase 2Wilson disease-associated proteinWNDPWDWC1Copper pump 2ATPase, Cu++ transporting, beta polypeptideATPase copper transporting polypeptide beta

In Wilson disease, therapeutic strategies focus on copper removal via chelation (e.g., penicillamine) or blocking intestinal absorption via zinc salts; gene therapies aim to restore functional ATP7B protein expression in hepatocytes [8, 10]. In oncology, ATP7B inhibition (e.g., via siRNA) is used to prevent the sequestration and efflux of platinum-based drugs, thereby increasing intracellular drug concentration and sensitizing cancer cells to chemotherapy [1, 3].