Tau, a microtubule-associated protein, is known for its significant involvement in neurodegenerative diseases. While various molecular and immunohistochemical techniques have confirmed the presence of Tau in podocytes, its precise function within these cells remains elusive. In this study, we investigate the role of Tau in kidney podocytes using Drosophila pericardial nephrocytes as a model. We found that knockdown of Drosophila Tau in nephrocytes resulted in apoptotic cell death and the disruption of nephrocyte structure. Furthermore, we observed that decreased Tau levels induced genomic damage and abnormal distribution of γ-H2Av, altering nuclei architecture in nephrocytes, and affecting the nuclear membrane structure by interfering with lamin with aging. Additionally, Tau knockdown led to a reduction in lipid droplets in Drosophila fat body tissues, suggesting a potential role of Tau in inter-organ communication. These findings underscore the importance of Tau in the nephrocytes of Drosophila, and advocate further research to broaden our understanding of podocyte biology in kidney diseases. [BMB Reports 2025; 58(4): 169-174].