Thus, since several mutations affecting the functional domains of p62 have been identified in patients with ALS and frontotemporal dementia, it has been demonstrated that p62 variants exhibit reduced KEAP1-binding, preventing NRF2 from entering the nucleus and promoting protective genes, and predisposing the cell death upon exposure to ROS [250, 251]. Here, SQSTM1 is linked to amyotrophic lateral sclerosis.