Phytophthora palmivora is a devastating oomycete plant pathogen. We found that P. palmivora induces disease in Lotus japonicus and used this interaction to identify cellular and molecular events in response to this broad host range oomycete. Transcript quantification revealed that Lys12 was highly and rapidly induced during P. palmivora infection. Mutants of Lys12 displayed an accelerated disease progression, earlier plant death, and lower level of defense gene expression, while the defense program after chitin, laminarin, oligogalacturonide or flg22 treatment, or the root symbioses with nitrogen-fixing rhizobia and arbuscular mycorrhiza were similar to wild-type. On the microbe side, we found that P. palmivora encodes an active chitin synthase-like gene, and mycelial growth is impaired after treatment with a chitin-synthase inhibitor. However, Wheat Germ Agglutinin-detectable N-acetyl-glucosamin (GlcNAc) epitopes were not identified when grown in vitro or while infecting the roots. This indicates that conventional GlcNAc-mers are unlikely to be produced and/or accumulate in P. palmivora cell walls and that LYS12 might perceive an unknown carbohydrate. The impact of Lys12 on progression of root rot disease, together with the finding that similar genes are present in other P. palmivora hosts suggests that LYS12 might mediate a common, early response to this pathogen. This article is protected by copyright. All rights reserved.