Because of the common eukaryotic origin of fungi and mammals, the development of new antifungal drugs has been challenging. This may be the reason for the introduction of only five classes of antifungal agents, including fluorinated pyrimidine analogs, polyenes, allylamines, azoles, and echinocandins. Here, we have tried to find some novel drug targets against A. fumigatus using bioinformatics. Our alignment has demonstrated a group of proteins/genes (Table 2) that are fungal-specific and may be essential to A. fumigatus. Our highlights differ from other studies such as Abadio and colleagues in comparative alignment as we searched for those novel targets that only exist in A. fumigatus. In this study, we found a RNA-binding protein (AfuRBP) that has been annotated as a member of PPI enzyme family. The PPI family contains three members, including cyclophilins, FKBPs, and Parvulin. Cyclophilins are described by an eight-standard β-barrel that forms a hydrophobic pocket. FKBPs, instead, contain an amphipatic, five-stranded β-sheet that enfolds around a single, short α-helix[25, 26]. Members of Parvulin family contain a PPI domain consisting of a half β-barrel and its four antiparallel strands surrounded by four α-helices. The results of I-TASSER modeling and docking demonstrated that the AfuRBP is structurally closer to Parvulin family members of PPI enzyme family. To elucidate the function of this protein, AfuRbp-deficient strains were generated using gene deletion and RNAi strategies. Normal phenotype of these strains indicated a non-essential role for this protein in growth physiology of Aspergillus fumigatus. Some studies have demonstrated that the inactivation of a drug target gene can result in increased sensitivity of the organism to the drug or other compounds that inhibit the same pathway[27, 28]. In this sense, the sensitivity of AfuRbp-disrupted strains to PPI inhibitors was assessed.