An ALS/FTD-causing pathogenic mutation in cyclin F at amino acid position 621 from serine to glycine (Cyclin F-S621G) was shown to increase the specific ubiquitination at lysine-48 of proteins, which led to the accumulation of lysine-48-ubiquitinated proteins and the impairment of autophagic degradation [199], indicating autophagy to be a degradative mechanism underlying the pathogenesis of ALS/FTD. Here, CCNF is linked to amyotrophic lateral sclerosis.