The rpg4-mediated resistance locus (RMRL) in barley provides recessive resistance against wheat stem rust (Puccinia graminis f. sp. tritici) races including the virulent race TTKSK (a.k.a Ug99). Three genes (HvAdfF3, Rpg5, and HvRga1) at the RMRL are required together for resistance. Allele characterization of these three genes identified the dominant rye stem rust resistance gene Rpg5 gene as the polymorphic R-gene conditioning the recessive rpg4-mediated wheat stem rust resistance. The Rpg5 gene contains an atypical R-gene structure encoding a nucleotide-binding site, leucine rich repeat, and serine/threonine protein kinase (STPK) domains. Genetic analysis of crosses between the resistant cultivar Q21861 with a functional Rpg5 allele and different susceptible varieties determined that most susceptible cultivars contain the susceptibility gene HvPP2C.1 in place of Rpg5 STPK domain. Genetic analyses determined that HvPP2C.1 conditions the recessive nature of the reaction, possibly negatively regulating the signaling pathway initiated by the Rpg5 kinase domain.