INTRODUCTION: Tuberculosis (TB), caused by METHODS: We explored the roles of PE18 and PPE26 using recombinant RESULTS: Our biochemical analyses confirmed interactions between PE18/PPE26, PE18/PPE27, PE19/PPE25, and EspG5/PPE, highlighting their involvement in ESX-5-mediated secretion. Cell fractionation studies revealed that PE/PPE proteins predominantly localize to the cell wall, with PE18 also secreted extracellularly. In vitro and DISCUSSION: Our findings elucidate the pivotal roles of PE18 and PPE26 in