Purpose <p><i>Rhipicephalus microplus</i> is a bovine ectoparasite that causes economic losses due to direct damage to the host, the cost of treatments, and the transmission of diverse pathogens. We have previously identified the protein VDAC (BmVDAC) from the midgut of <i>R. microplus</i>. Furthermore, we demonstrated the efficacy of BmVDAC in a bovine vaccination trial. Additionally, BmVDAC interacts with the sexual stages of <i>Babesia bigemina</i>, and its expression increases in ticks during infection with the parasite. Hence, we are interested in studying the function of this protein.</p> Methods <p>Molecular docking was used to predict that BmVDAC binds to the Kringle 5 (K5) domain of plasminogen, ligand blotting techniques, and inhibition of binding assays with the lysine analog εACA were performed to demonstrate the specificity of the binding.</p> Results <p>The docking analysis predicted the binding of the BmVDAC to the K5 domain, with a lysine participating in this interaction. The ligand blotting and inhibition assays demonstrated the specificity of the binding of the two proteins. Additionally, the results of a plasminogen activation assay showed that BmVDAC increases plasminogen activation.</p> Conclusion <p>This is the first report of a VDAC protein from a nonmammalian organism that interacts with and enhances the activation of plasminogen. The results indicate that the binding of the two proteins is specific, and the binding of BmVDAC promotes the conversion of plasminogen into active plasmin.</p>