Consistently, overexpression of Cyclin-F carrying the ALS linked S621G mutation was reported to increase ubiquitination in general and in particular ubiquitination of the known SCFCyclin-F target RRM2 and of the neuropathological ALS marker RNA-binding protein TDP43 in combination with UPS and autophagy impairments (24, 25). This evidence concerns the gene RRM2 and amyotrophic lateral sclerosis.