Indeed, we find examples of genetic deficiencies in extracellular RNases that lead to immune-related diseases, such as amyotrophic lateral sclerosis (ALS), associated with human RNase5 mutations (21, 22) and cystic leukoencephalopathy, a neuronal disorder associated with RNaseT2 deficiency (23, 24). Here, RNASET2 is linked to amyotrophic lateral sclerosis.