RAN and amyotrophic lateral sclerosis: It is notable that pt #78 came to medical attention early in her clinical course, prior to serious disability, and yet, the signature changes (lowered p62 and elevated RanGTPase 17 kDa fragment) were nevertheless observed, and sadly, progressed with worsening of ALS, culminating in her death, approximately 2 years after initial detection of the Ran 17 kDa fragment as shown in Fig. 5, together with the reciprocal change in p62/SQSTM1, seen exacerbated over time.