found that ISG15 positively correlated with the degree of neuronal injury in animal models of ALS with no obvious signs of inflammation, a model cerebral ischemia, a model of cortical shock-induced brain injury, and a mouse model of chronic neuronal injury caused by the viral protein HIV gp120, with low levels of ISG15 in unaffected areas and high levels of ISG15 in neuronal injury areas. Here, ISG15 is linked to amyotrophic lateral sclerosis.