Rice blast caused by Magnaporthe oryzae is one of the most devastating plant diseases in the world, which frequently leads to an enormous yield loss. Cultivation of rice cultivars carrying resistance (R) genes is an effective, economical and ecologically sound approach to prevent the rice blast disease. Recently, we have isolated and functionally validated the broad-spectrum blast resistance gene Ptr, which encodes an atypical R protein without nucleotide binding site-leucine rich repeat (NLR) domains. In this study, a combination of molecular, biochemical and genetic approaches is being taken to elucidate the underlying mechanism of the Ptr-mediated rice blast resistance. A number of the Ptr-interacting proteins have been identified by the yeast two-hybrid screening and predicted protein interactions. These putative interacting proteins are being validated using in vitro protein pull-down and in vivo co-immunoprecipitation and bimolecular fluorescence complementation. Further molecular and genetic characterization of these interacting proteins is expected to help elucidate the molecular and biochemical basis of the Ptr-mediated blast resistance and facilitate the precision breeding of new rice cultivars with durable and broad-spectrum blast resistance.