E3 ligase complex SCFcyclinF ubiquitylates p62 at K281, promoting the aggregation of p62 into the insoluble, whereas mutant cyclin F promotes aberrant p62 ubiquitination and insolubility in ALS and frontotemporal dementia (FTD) Pathogenesis [121]. Here, SQSTM1 is linked to amyotrophic lateral sclerosis.