C9orf72 and amyotrophic lateral sclerosis: Despite this, much evidence has been collected to assert that loss of endogenous C9orf72 protein alone is not sufficient to induce the neurodegeneration characteristic of ALS and FTD, instead, a combination of loss-of-function and gain-of-function is more likely (Braems et al., 2020; Pal et al., 2021).