Interestingly, an abnormal increase in the ubiquitination of TDP-43 was detected in neuronal cells overexpressing mutant cyclin F (Williams et al., 2016), suggesting that CCNF mutations modify the activity of the SCF, therefore impairing the degradation of aberrant ubiquitinated proteins and promoting their aggregation in ALS and FTD patients. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.