Salicylic acid (SA) is a pivotal plant hormone for plant immunity, but our knowledge of microbe-induced SA signaling among plant species is limited, primarily relying on Arabidopsis thaliana research. Exciting recent findings at the Goossens lab revealed a novel SA signaling pathway in tomato, dubbed the NIS pathway, acting alongside the NPR1-dependent pathway. Despite its potential significance for understanding immunity in dicot species, the identity and functions of the receptor of SA in the NIS pathway remain elusive, forming the primary objective of this proposal. To achieve this, I will employ the well-established CRISPR/Cas9-based reverse genetic screen on a rational set of target candidates identified through comprehensive homology searches, genome-wide protein-metabolite studies, and protein-protein interactomics approaches. Further exploration of the biochemical and structural aspects of the SA receptor will be conducted to gain insights into the molecular mode of action by which SA is perceived. Additionally, the importance of the NIS and NPR pathways in tomato resilience against diverse microbial pathogens will be investigated through artificial infections in edited tomato plants. Overall, this research aims to provide a comprehensive understanding of the novel SA receptor in tomato immunity, offering insights that could have broad implications for enhancing stress resilience in crops and contributing to advancements in agricultural practices and food security.