Although TGF-β1 signaling through the Smad-based (canonical) pathway5–7 is believed to play a critical role in the development of renal fibrosis, a growing body of evidence indicates that several non-Smad (non-canonical) pathways stimulated by TGF-β1 are also potentially involved in driving fibrosis in progressive kidney disease8–10. The gene discussed is TGFB1; the disease is renal fibrosis.