Powdery mildew is a common serious disease threatening global melon production. Red light can improve plant resistance to powdery mildew by inducing endogenous ethylene synthesis
however, the underlying molecular mechanism requires elucidation. In this study, an ERF transcription factor CmRAP2-13 was identified, silencing it significantly improved melon seedlings resistance to powdery mildew. Further research found that CmRAP2-13 inhibited the expression of key ethylene synthesis genes CmACS10 and CmERF27 by binding to GCC-box in the promoters, thus inhibiting ethylene biosynthesis. At the same time, protein-level interaction between CmRAP2-13 and CmERF27 also occurred. When CmRAP2-13 existed, the transcriptional activation of CmERF27 on CmACS10 was interfered and weakened. However, red light pretreatment notably decreased the expression of CmRAP2-13, and this process was influenced by phytochrome B, the red light receptor. Analysis of defence-related gene expression following ethephon application and CmRAP2-13 silencing revealed that CmRAP2-13 acted as a negative regulator of melon seedling resistance to powdery mildew, functioning as a convergence point for red light and ethylene signalling. Taken together, red light induced CmRAP2-13 and played a negative role in regulating Podosphaera xanthii infection in melons. Powdery mildew infection produced ethylene, which further inhibited CmRAP2-13 expression and formed a feedback regulation loop to participate in disease resistance. Our research on CmRAP2-13 deciphers the important regulatory network of red light-induced ethylene production in melon powdery mildew resistance, which can be used as a potential target of genetic engineering to enhance plant protection against powdery mildew.