In amyotrophic lateral sclerosis (ALS), a neuromuscular neurodegenerative disorder that causes gradual loss of motor neurons, overexpression of TDP-43, one of the thought initiators of disease, dampens the ER to mitochondria apposition via the VAPB-PTPIP51 tethering complex (Stoica et al., 2014). Here, VAPB is linked to amyotrophic lateral sclerosis.