Our findings provide new insight on the immune response happening in cutaneous leishmaniasis, sheer light on the mechanism behind the host-pathogen interaction occurring in the initial moments of infection, putting GP63 and Leishmania spp.-derived EVs in the center of this battle, thus creating the opportunity of using them as the target of new pharmacological treatments and vaccinations. The gene discussed is LMLN; the disease is cutaneous leishmaniasis.