Fusarium oxysporum causes Fusarium wilt disease in many agricultural important crops. To understand how the fungus manipulates its hosts we identify the targets of its Secreted in Xylem (SIX) effectors. Previously we reported that SIX3 (Avr2) targets PAMP triggered immunity by compromising the function of BIK1 (Blekemolen et al., 2023 MPP). SIX5 modulates the size exclusion limit of plasmodesmata allowing symplastic spread of SIX proteins such as SIX8 (Talbi et al., 2023 MPP; 37, 304, Blekemolen et al., 2022 FPS;13). The broadly conserved SIX8 effector targets specific members of the Topless (TPL) family (Aalders et al., 2024 PBJ; 22, 248). Tomato tpl1/tpl2 mutants and Arabidopsis thaliana tpr1/tpl double mutants show resistance to Fusarium wilt, designating TPLs as genuine S genes....