Multiple studies have shown that activation of the NMD pathway, particularly via activation of UPF-1, can modify C9orf72 neurotoxicity through a reduction in DPR levels, leading to neuroprotective effects in several in vitro and in vivo models of C9ALS/FTD (Xu et al, 2019; Ortega et al, 2020; Sun et al, 2020; Zaepfel et al, 2021). Here, UPF1 is linked to frontotemporal dementia.