While JNK has been shown to phosphorylate Smad3 to enhance the fibrotic response in short term AA stimulation of tubular epithelial cells (Zhou et al., 2010a), and combined JNK and Smad3 inhibition gives additive benefit in reducing folic acid-induced renal fibrosis (Jiang et al., 2019); it may that chronic administration of AA drives a Smad3-dependent fibrosis that is largely independent of JNK signaling. The gene discussed is SMAD3; the disease is renal fibrosis.