Identification of TaS3 as a potential susceptibility gene encoding a protein homologous to ULP1 protease in wheat, which may regulate SUMO function facilitating powdery mildew attack. Some plant genes that are required for susceptibilities to certain pathogens are known as susceptibility genes or susceptibility factors, whose loss-of-function mutations can confer the plants resistances. To identify potential susceptibility genes to powdery mildew in wheat, differentially expressed genes in compatible and incompatible interactions between wheat and powdery mildew were examined by the cDNA chip assay. The genes exclusively expressed in the susceptible cultivar were interfered using biolistic transient transformation in wheat epidermal cells. The suppression of gene TaS3 (Triticum aestivum susceptibility) decreased the pathogen penetration by 19%, and its over-expression increased the disease susceptibility. The deduced protein from TaS3 belongs to the putative ubiquitin-like protease 1 peptidase domain family. Subcellular localization studies revealed that its protein was accumulated in the nucleus. Quantitative real-time polymerase chain reaction analysis revealed that TaS3 transcript was significantly induced in the compatible host. This suggests that TaS3 is a potential susceptible gene and its function may be related to regulate SUMO functions.