Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors detect pathogen effectors and activate immunity1. Coiled-coil NLRs (CNLs) form resistosomes as Ca2+-permeable channels in the plasma membrane (PM)2–4. However, the mechanism by which resistosomes activate cell death remains unclear. Here we report that the CNL SUPPRESSOR OF mkk1 mkk2 2 (SUMM2), unlike canonical CNLs that use a MADA motif to penetrate the PM5, tethers to the PM through N-myristoylation, a common feature among many CNLs. PM targeting via N-myristoylation is essential for SUMM2-induced cell death. Upon activation, SUMM2 promotes the association of the lipase-like proteins ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) and PHYTOALEXIN DEFICIENT 4 (PAD4) with the helper NLR-ACTIVATED DISEASE RESISTANCE 1-LIKE 1 (ADR1-L1). Furthermore, active SUMM2 induces the clustering of multiple ADR1-L1 resistosomes into a ring-like assembly colocalized with the EDS1–PAD4 complex, and the EDS1–PAD4–ADR1 module is essential for SUMM2-activated cell death. Together, these findings reveal that N-myristoylation-mediated PM targeting of SUMM2 promotes the assembly of higher-order EDS1–PAD4–ADR1-L1 resistosome clusters for cell death initiation.
