Copper-transporting ATPase 2 (ATP7B) (ATP7B)

Copper-transporting ATPase 2 (ATP7B) is a critical transmembrane protein belonging to the P-type ATPase family, primarily localized in the hepatocytes of the liver and also found in the brain and kidneys [1, 2]. Its primary biological function is to maintain copper homeostasis by transporting copper ions from the cytosol into the trans-Golgi network for incorporation into ceruloplasmin or by sequestering excess copper into vesicles for biliary excretion [3]. Mutations in the ATP7B gene lead to Wilson disease, a rare genetic disorder where copper accumulates to toxic levels in the liver and central nervous system, causing hepatic failure and neuropsychiatric symptoms [1, 4]. In the context of oncology, ATP7B is also recognized for its role in mediating resistance to platinum-based chemotherapies, such as cisplatin, by facilitating the efflux of these drugs from tumor cells [3]. Current therapeutic development focuses on gene therapy candidates like VTX-801 and UX701, which aim to deliver a functional copy of the ATP7B gene to restore normal copper metabolism [5, 6]. Additionally, research into pharmacological chaperones seeks to correct the misfolding of specific ATP7B mutants to restore their transport activity [4].

Other names

Wilson disease-associated proteinWNDP-type copper-transporting ATPase 2ATPase Cu++ transporting beta polypeptideWilson disease protein

Gene replacement therapy to restore functional copper transport; Pharmacological chaperoning to stabilize and traffic mutant ATP7B; Substrate-mediated efflux of platinum-based drugs.