Here we present an overview of our existing knowledge on the function of RIN4 as a regulator of plant defense and as a guardee of multiple plant R-proteins. Domain analysis of RIN4 reveals two NOI domains. The NOI domain was originally identified in a screen for nitrate induced genes. The domain is comprised of approximately 30 amino acids and contains 2 conserved motifs (PXFGXW and Y/FTXXF). The NOI gene family contains members exclusively from the plant lineage as far back as moss. In addition to the conserved NOI domain, members within the family also contain conserved C-terminal cysteine residue(s) which are sites for acylation and membrane tethering. Other than these two characteristic features, the sequence of the family of NOI-containing proteins is diverse and, with the exception of RIN4, their functions are not known. Recently published interactome data showing interactions between RIN4 and components of the exocyst complex prompt us to raise the hypothesis that RIN4 might be involved in defense associated vesicle trafficking.