Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with both motor and cognitive symptoms. At present, no treatments exist to modify the rapidly progressive course of either the motor or cognitive symptoms of the disease. The goal of the present study is to study a recently developed animal model of ALS utilizing the Human Endogenous Retrovirus-K (HERV-K) envelope (env) protein which has been shown to be toxic to motor neurons. Approximately one-third of ALS patients seen at the NIH Clinical Center have evidence of active HERV-K RNA transcription. Utilizing electrophysiology techniques, imaging, and RNA sequencing, we endeavor to highlight the role HERV-K plays in modifying neuronal function at the level of the synapse and identify potential druggable targets to ameliorate the neurotoxicity of HERV-K.