OPTN and frontotemporal dementia: 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.