Vph2 is a putative V-ATPase assembly factor. Our previous study has characterized its roles in localization of V-ATPase subunit, cell wall composition, hyphal development and virulence. In this study, our results further demonstrated that Vph2 was localized around the nucleus and in patches close to the periphery of the cell, indicating that Vph2 was located to the endoplasmic reticulum (ER), which was consistent with that in Saccharomyces cerevisiae. Disruption of VPH2 led to hypersensitivity to reducing stresses induced by dithiothreitol (DTT) and beta-mercaptoethanol (beta-ME), and displayed increased GSH content and up-regulation of unfolded protein response (UPR)-related genes, such as PRBI and PMT4. However, the induced UPR and growth defect on beta-ME plates of vph2(sic)/(sic) mutant could be partly alleviated by the GSH-specific scavenger 1-chloro-2, 4-dinitrobenzene (CDNB). These results indicated that loss of VPH2 led to an increase in GSH levels, which induced the UPR and caused the defective growth on reductive stress induced by beta-ME. In summary, Vph2 is necessary to maintain resistance against reductive stresses. (C) 2019 Elsevier Inc. All rights reserved.