ABSTRACTS.J. Jensen, Z.C. Ruhe, A.F. Williams, D.Q. Nhan, et al. (J Bacteriol 205:e00113-23, 2023,https://doi.org/10.1128/jb.00113-23) demonstrate that a type VI secretion system (T6SS) immunity protein, Tli, functions to both neutralize and activate its cognate toxin, Tle, inEnterobacter cloacae. Their results reveal the surprising finding that Tli function differs, depending on its subcellular localization. Overall, this study enhances our understanding of T6SS immunity proteins, which are commonly viewed as monofunctional toxin-neutralizing antidotes.