Hence, we aimed to examine the effects of pathogenic CCNF on these pathways using induced pluripotent stem cell (iPSC)-derived motor neurons from a symptomatic CCNFS621G ALS patient or healthy control, Ub proteomics and mutants that disrupt the ability of CCNF to form an active Ub ligase complex, coupled with reporters of UPS function and Ub homeostasis. Here, CCNF is linked to amyotrophic lateral sclerosis.