For example, recessive mutations in senataxin (SETX, a protein that protects the replication fork across the RNA-Polymerase-II-transcribed gene and unwinds unnecessary R-loops) cause R loop accumulation [35] in a particular type of ALS (ALS4) and Ataxia with oculomotor apraxia type 2 (AOA2) [7,109,110]. Here, SETX is linked to amyotrophic lateral sclerosis.