Background: Proteinuria is a sensitive hallmark for progressive renal dysfunction. Transgelin (TAGLN) has been demonstrated to participate in etiology of proteinuria and dynamics of podocyte foot process; however, the mechanism of TAGLN involvement in proteinuria is unknown. The present study aimed to explore the roles of TAGLN in the development of proteinuria. Methods: Differentially expressed genes (DEGs) were detected from microarray expression profiling datasets from Gene Expression Omnibus, and analyzed by the short time series expression miner to cluster the DEGs in proteinuria progression. Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to determine the top 20 enriched pathways, and construct a gene interaction network. Results: In total, 2,409 DEGs for nephropathy and 10,612 DEGs for podocyte foot process and proteinuria were detected. Additionally, 76 common DEGs (25 upregulated and 41 downregulated) between nephropathy and podocyte foot process were primarily involved in innate immunity, positive regulation of transcription-DNA-templated, immunity and negative regulation of cell proliferation, enriched in cytokinecytokine receptor interaction signaling pathway, Ras signaling pathway, axon guidance, tumor necrosis factor (TNF) signaling pathway and apoptosis. Conclusions: We discovered a TAGLN-mediated regulatory network involved in proteinuria progression. These findings provide novel insight to understand the molecular mechanisms underlying the pathogenesis of proteinuria.