Also, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), the toxic aggregation of one protein – TDP-43 – can result from defects in other proteins, some of which are related to proteostasis, such as the shuttle protein Optineurin and the E3 ubiquitin ligase VCP. Here, OPTN is linked to amyotrophic lateral sclerosis.