TARDBP and frontotemporal dementia: While heterozygous mutations of GRN cause an adult age onset FTD with ubiquitinated TDP-43 inclusions and behavioural, agrammatism and motor speech deficits (bvFTD, nfvPPA) (Ferrari et al., 2019), homozygous GRN mutations produce a different and more aggressive juvenile onset of a LSD known as neural ceroid lipofuscinosis (NCL), characterized by abnormal lipopigment deposition in dysfunctional lysosomes (Mole et al., 2019) (Figure 3).