Following detection of pathogen cognate effectors, plant Nod-like receptors (NLRs) trigger isolate-specific immunity that is generally associated with cell death. Regulation of NLR stability is important to ensure effective immunity. In barley, the allelic MLA receptors mediate isolate-specific disease resistance against powdery mildew fungus (Blumeria graminis f. sp. hordei; Bgh). Currently, how MLA stability is controlled remains unknown. Here, we identified a MLA interacting RING-type E3 ligase, MIR1, that interacts with several MLAs. We showed that the C-terminal TPR domain of MIR1 mediates the interaction with the CC-domain-containing region of functional MLAs, such as MLA1, MLA6 and MLA10, but not with that of the non-functional MLA18-1. MIR1 can ubiquitinate the N-terminal region of MLAs in vitro and promotes proteasomal degradation of MLAs in vitro and in planta. Both proteasome inhibitor treatment and VIGS-mediated MIR1 silencing significantly increased MLA abundance in barley transgenic lines. Furthermore, overexpression of MIR1 specifically compromised MLA-mediated disease resistance in barley, while co-expression of MIR1 and MLA10 attenuated MLA10-induced cell death signaling in Nicotiana benthamiana. Together, our data reveal a mechanism for control of the stability of MLA immune receptors and for the attenuation of MLA-triggered defense signaling by a RING-type E3 ligase via the ubiquitin proteasome system.