Multiple studies suggest that inhibitory neurons are involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS and FTD are two devastating, frequently co-occurring neurodegenerative disorders. While ALS primarily affects motor neurons, causing rapid progressive paralysis and premature death, FTD affects frontal and temporal lobes, leading to severe changes in personality, behaviour, or language skills. To characterise the contribution of inhibitory neurons to these phenotypes, we generated a mouse model based on the expression of mutant Fused in Sarcoma (FUS) selectively in GABAergic neurons. Homozygous mice showed a progressive alteration of postnatal body development, as evidenced by reduced weight and limb strength. Additionally, half of the homozygous pups died before weaning. We are now investigating whether these phenotypes are linked to excitation/inhibition imbalance or growth delay. Heterozygous males displayed social abnormalities at 4 and 10 months of age. To pinpoint the underlying mechanisms, we conducted in vivo two-photon calcium imaging, where we observed an increase in neuronal activity levels in the frontal cortex of anesthetized animals. Our results indicate that FUS mislocalisation in inhibitory neurons is sufficient to cause cortical hyperexcitability and FTD-like impairments. As a complementary strategy, we developed a mouse model expressing mutant FUS in every cell type except inhibitory neurons. Our genetic rescue approach was effective in reducing FTD-like social defects in males and delaying ALS-like motor defects in females. Ultimately, we aim to determine how the expression of mutant FUS in inhibitory neurons contributes to their dysfunction and the development of ALS- and FTD-like symptoms.