If, as reported in patients with liver cirrhosis, the E3 ubiquitin ligase synoviolin (HRD1) is increased, leading to Nrf2 ubiquitylation and Keap1-independent Nrf2 degradation, then targeting HRD1 rather than Keap1 might be promising [191]. Here, NFE2L2 is linked to cirrhosis of liver.