Background: Fabry Nephropathy is a major cause of morbidity and premature death in patients with Fabry disease (FD) a rare X-linked lysosomal storage disorder.Gb3, the main substrate of α-gal A, progressively accumulates within cells in a variety of tissues. Establishment of cell models have been useful as a tool for testing hypotheses of disease pathogenesis. Methods: We applied CRISPR/Cas9 genome editing technology to the GLA gene to develop human kidney cell models of FD in human immortalized podocytes, which are the main affected renal cell type. Results: Our podocytes lack detectable α-gal A activity and have increased levels of Gb3. To explore different pathways that could have distinct patterns of activation under conditions of α-gal A deficiency, we used a high-throughput antibody array to perform phosphorylation profiling of CRISPR/Cas9-edited and control podocytes. Changes in both total protein levels and in phosphorylation status per site were observed. Conclusion: Analysis of our candidate proteins suggests that multiple signaling pathways are impaired in FD.