A pathway analysis of these genes did not provide evidence for a protective effect of PGRN on one specific pathway, it rather hinted at a pleiotropic effect of PGRN on different pathways, some with possible importance for ALS-FTD (Rsad2 is an ER stress-induced protein involved in cell defense, Top2a is a topoisomerase involved in replication- and transcription-associated DNA breaks and repair, Fbxo22 is part of the ubiquitin ligase complex involved in ubiquitination and degradation of proteins). Here, RSAD2 is linked to amyotrophic lateral sclerosis.