ENTPDases are enzymes known for hydrolyzing extracellular nucleotides and playing an essential
role in controlling the nucleotide signaling via nucleotide/purinergic receptors P2. Moreover,
ENTPDases, together with Ecto-5´-nucleotidase activity, affect the adenosine signaling via P1 receptors.
These signals control many biological processes, including the immune system. In this context, ATP is
considered as a trigger to inflammatory signaling, while adenosine (Ado) induces anti-inflammatory response.
The trypanosomatids Leishmania and Trypanosoma cruzi, pathogenic agents of Leishmaniasis
and Chagas Disease, respectively, have their own ENTPDases named “TpENTPDases,” which can affect
the nucleotide signaling, adhesion and infection, in order to favor the parasite. Besides,
TpENTPDases are essential for the parasite nutrition, since the Purine De Novo synthesis pathway is
absent in them, which makes these pathogens dependent on the intake of purines and nucleopurines for
the Salvage Pathway, in which TpENTPDases also take place. Here, we review information regarding
TpNTPDases, including their known biological roles and their effect on the purinergic signaling. We
also highlight the roles of these enzymes in parasite infection and their biotechnological applications,
while pointing to future developments.