Ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2) (ENTPD2)

Ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2), also known as CD39L1, is a membrane-bound enzyme that plays a pivotal role in the purinergic signaling cascade by hydrolyzing extracellular nucleoside triphosphates, particularly ATP, into their diphosphate forms like ADP [14, 16]. Unlike other members of the E-NTPDase family, such as CD39 (NTPDase1), ENTPD2 has a high preference for ATP over ADP, leading to the accumulation of extracellular ADP [16, 19]. This activity is critical in various physiological contexts, including the regulation of platelet activation, where the generated ADP activates P2Y receptors, and in the nervous system, where it modulates purinergic neurotransmission [11, 16]. In the context of oncology, ENTPD2 is frequently overexpressed in the tumor microenvironment of cancers such as hepatocellular carcinoma and gastrointestinal malignancies, where it contributes to immune evasion by depleting pro-inflammatory ATP [7, 10]. Therapeutic strategies targeting ENTPD2, such as the monoclonal antibody KAZ954, aim to inhibit its enzymatic activity to restore extracellular ATP levels and enhance anti-tumor immune responses [3, 7]. Additionally, ENTPD2 is being investigated for its roles in inflammatory diseases, neurodegeneration, and parasitic infections, making it a versatile target for drug development [6, 18, 19].

Other names

NTPDase 2CD39 antigen-like 1CD39L1Ecto-ATPaseEcto-ATPDase 2Ecto-ATPase 2

Inhibition of ATP hydrolase activity to increase extracellular ATP levels and stimulate anti-tumor immune responses [3, 7]; induction of antibody-dependent cellular cytotoxicity (ADCC) [7].