Immunoglobulin A nephropathy (IgAN) is an immune-complex-mediated glomerulonephritis characterized by the presence of IgA deposits in mesangial and paramesangial regions. However, the exact mechanism involved in IgA deposition is still unknown. TGF-β(1) that mediates the progression of IgAN is well established as a critical IgA class (isotype) switching factor, and Smad proteins are critical intracellular mediators in the expression of TGF-β(1)-targeted genes, which suggest that TGF-β signaling has been implicated in the primary pathogenesis of IgAN. Arkadia, an E3 ubiquitin ligase, can amplify TGF-β signaling through regulating Smads degradation. When these findings are considered together, it is of interest to explore how Arkadia and Smad signaling affect TGF-β(1)-induced IgA expression in IgAN. Therefore, we propose that Arkadia could positively contribute to TGF-β(1)-induced IgA secretion through up-regulation of Smad signaling in the pathogenesis of IgAN.