Abstract: Plants exploit a broad range of phylogenetically related cell surface proteins, termed Receptor Kinases (RKs), as sophisticated environmental sensors. RKs can recognize ‘self’ and ‘non-self’ signals in the extracellular space allowing plants to infer the current and future state of their local environment. RKs contain an extracellular domain (ECD), a single pass transmembrane domain, and a cytoplasmic kinase domain. ECDs serve as platforms for ligand binding and recruitment of regulatory modules. Understanding how interactions between extracellular domains produce signal-competent receptor complexes is challenging due to their transient nature and low biochemical tractability. The largest family of RKs in Arabidopsis consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR-RKs), crucial for the sensing of microorganisms, cell expansion, stomata development and stem-cell maintenance. While principles governing LRR-RK signalling activation are arising, the systems-level organization of this family of proteins is totally unexplored. Here, I will present how using a sensitized high-throughput interaction assay, 40,000 potential extracellular domain interactions were interrogated to produce an LRR-based cell surface interaction network (CSILRR) comprising 567 interactions. I will then describe how the functions of previously uncharacterized LRR-RKs (APEX and APEX-2) in plant development and immunity, were predicted and validated. Finally, I will show that CSILRR operates as a unified regulatory network in which the LRR-RKs most critical for its overall structure are required to prevent aberrant signalling of receptors that are at several network-steps away.