The ubiquitin proteasome system (UPS) is critical for regulating different aspects of plant immunity, mostly through mediating the ubiquitination and further degradation of its protein substrates. To identify novel E3 ligases functioning as immunity regulators, we carried out a reverse genetic screen in Arabidopsis thaliana on selected candidate E3 ligase-encoding genes to identify the ones with altered immune responses when overexpressed. One of the genes, SNIPER5, causes autoimmunity-associated phenotypes when overexpressed, which include dwarfed stature, dark green curly leaf, highly-elevated PATHOGENESIS-RELATED (PR) gene expression, and enhanced resistance against plant pathogens. Conversely, loss-of-function mutants of sniper5 showed enhanced disease susceptibility against bacterial pathogen Pseudomonas syringae. Interestingly, the enhanced susceptibility of sniper5 mutants is partially due to reduced accumulation of salicylic acid. Ongoing research focuses on the identification of the ubiquitination target of SNIPER5 via various approaches, which will reveal the detailed mechanism on how SNIPER5 regulates plant immune signaling.