• Decreased levels of the trans-synaptic organizer neuronal pentraxin receptor (NPTXR) in C9-FTD vs. C9-NRE carriers, which is a trans-synaptic organizer of excitatory and inhibitory synapses (Barschke et al., 2020)• Pre-symptomatic C9-NRE mutation carriers, PET imaging with [11C] UCB-J, which binds to the synaptic vesicle protein, SV2A, revealed a synaptic loss in the thalamus before symptom onset (Malpetti et al., 2021). Here, NPTXR is linked to frontotemporal dementia.