Plants have evolved resistance (R) proteins to detect pathogen effectors and trigger plant defense responses in the so named effector-triggered immunity (ETI). R proteins are under negative regulation in plants as upregulated activation of R protein is detrimental to plant growth. Autoimmune mutants have been instrumental in understanding the fine tuning of plant defense responses. Recently, a number of such mutants have been molecularly characterized, and some of them result from over-activation of SNC1, a TIR-NBS-LRR type of R protein. Studies of these mutants revealed a complex negative regulation of SNC1 activity from transcriptional to post-translational regulation. Here, we summarize studies on these SNC1-dependent auto-immune mutants and discuss the fine regulation of R proteins in plant immunity.