Receptors typically exhibit high specificity for ligands with which they interact, but cells also contain co-receptors and regulatory proteins that function together with receptors and do not necessarily exhibit specificity for only a single type of ligand. These co-receptors and regulatory proteins can be important facilitators or suppressors of signaling activation. They also allow signaling crosstalk at the plasma membrane, helping to coordinate appropriate downstream signaling in the presence of diverse endogenous and exogenous extracellular ligands. Important examples of regulatory/co-receptor RLKs include the SERK family members, BIR family members and SOBIR1. SERK proteins have been identified in many different plant species. In Arabidopsis the family consists of five members. They all have five LRRs in their ectodomain, share high overall sequence similarity and have redundant functions to various degrees. SERK proteins have been shown to be involved in plant immunity in Arabidopsis, tomato and rice, through interactions with the receptors FLS2, EFR, PEPR1, PEPR2, Xa21, Ve1 and Eix1. The BAK1 co-receptor also contributes to somatic embryogenesis and to plant development through interaction with the brassinolide hormone receptor BRI1. Despite impressive progress, much remains unknown about how the SERK proteins participate in all these different cell signaling tasks, and about the LEE011 spatial expression of SERK proteins. Studies of the SERK proteins are impeded by the redundant functions among family members and by pleiotropic effects when multiple SERK proteins are knocked out. As an example, bak12 Arabidopsis plants only have partially disrupted FLS2 signaling outputs. A possible means of circumventing this problem of SERK functional redundancy, adopted in the present study, is to identify the specific SERK interaction site of a partner receptor and then mutate that site. If all SERKs interact with a specific receptor at similar amino acids, this approach should impair the interaction of the receptor with all SERK family members. Recent X-ray crystallography studies provided detailed insight into the interaction of the ectodomain of BAK1 with the ectodomains of FLS2 and BRI1, and the interaction of the ectodomains of SERK1 and BRI1. In all three cases the respective ligand promotes interaction between the ectodomains of the main receptors and the SERK co-receptors. The ligand binds to the LRR domain of the main receptor, but the LRR domain of the SERK co-receptor also has multiple direct contacts with the ligand. It is surprising to see these fine-tuned co-receptor/ligand interactions, considering how many different known and potential unknown receptors and ligands BAK1 and SERK1 are able to interact with. Similar residues of the BAK1 and SERK1 ectodomains are involved in their interactions with FLS2 and BRI1.