SABP2 (Salicylic Acid Binding Protein 2) plays a vital role in the salicylic acid signaling pathway of plants both regarding basal resistance and systemic acquired resistance against pathogen infection. SIP-428 (SABP2 Interacting Protein-428) is a Silent information regulator 2 (SIR2) like deacetylase enzyme that physically interacts with SABP2 in a yeast two-hybrid interaction and confirmed independently by a GST pull-down assay. We demonstrated that SIP- 428 is an NAD+ dependent SIR2 deacetylase enzyme. Transgenic tobacco plants silenced in SIP- 428 expression via RNAi showed enhanced basal resistance to microbial pathogens. Moreover, these SIP-428-silenced lines also exhibited a robust induction of systemic acquired resistance. In contrast, the transgenic tobacco lines overexpressing SIP-428 showed compromised basal resistance and failed to induce systemic acquired resistance. These results indicate that SIP-428 is likely a negative regulator of SA-mediated plant immunity. Experiments using a SABP2 inhibitor showed that SIP-428 likely functions upstream of SABP2 in the salicylic acid signaling pathway. It also indicates that SABP2 is dependent on SIP-428 for its role in the SA signaling pathway. Subcellular localization studies using confocal microscopy and subcellular fractionation showed that SIP-428 localized in the mitochondria. These results clearly show a role for SIP-428 in plant immunity.