Mice overexpressing mutated forms of two RNA-DNA binding proteins commonly associated with ALS display overt synaptic defects: TDP-43 A315T mice have progressive loss of spines from P60–P90 compared to wild type mice (Handley et al., 2017) and FUS R521G mice have a significantly lower density of mature spines in the cortex at P18 (Sephton et al., 2014). Here, TARDBP is linked to amyotrophic lateral sclerosis.