Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. In Arabidopsis , a subfamily of "helper" NLRs is required by many "sensor" NLRs. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta, and conferred cytoplasmic calcium ion (Ca²⁺ ) influx in plant and human cells. NRG1.1-dependent Ca²⁺ influx and cell death were sensitive to Ca²⁺ channel blockers and were suppressed by mutations affecting oligomerization or plasma membrane enrichment. Ca²⁺ influx and cell death mediated by NRG1.1 and ACTIVATED DISEASE RESISTANCE 1 (ADR1), another helper NLR, required conserved negatively charged N-terminal residues. Whole-cell voltage-clamp recordings demonstrated that Arabidopsis helper NLRs form Ca²⁺ -permeable cation channels to directly regulate cytoplasmic Ca²⁺ levels and consequent cell death. Thus, helper NLRs transduce cell death signals directly.