Trypanosoma cruzi calreticulin (TcCalr), similar to calreticulin from other species, including human (HuCALR), is a multifunctional endoplasmic reticulum-resident chaperone, that the parasite translocates to the extracellular environment, where TcCalr participates in C evasion and infection, with important consequences in virulence. Here, CALR is linked to infection.