While dominant acting variants in OPTN appeared to make a substantial contribution to sporadic ALS, Pottier et al. first reported OPTN mutations in FTD, with their findings supporting a more complex mode of inheritance: sporadic individuals with heterozygous OPTN mutations who develop symptoms may do so because of compound heterozygote mutations (with the second hit not “qualifying” as a pathogenic variant) or because they also carry a mutation(s) in another gene (11). The gene discussed is OPTN; the disease is frontotemporal dementia.