A novel gain-of-function mutant showing dwarfism and bushy inflorescences was isolated from Arabidopsis activation-tagging lines. Transformed plants, in which the gene responsible for the phenotype of the mutant was overexpressed, exhibited phenotypes similar to constitutive systematic acquired resistance (SAR)-like defense responses including simulation of lesions in leaves and a highly activated PATHOGENESIS-RELATED 1 gene. We, therefore, designated the gene as DWARF AND LESION FORMATION 1 (DLE1) and showed it encodes a DUF 247 protein. Microarray and gene ontology analyses revealed that defense response genes, especially to biotic stimulus, were enriched in DLE1 overexpressing plants. Fusion proteins of the N-terminal fragment of DLE1 and GFP were likely to be localized in the endoplasmic reticulum (ER) in tobacco BY-2 cells. DLE1 may function in the plant defense system responding to environmental stimuli including biotic stresses in the ER. © 2013 The Japanese Society for Plant Cell and Molecular Biology.