There is limited research on the effects of Repressor Element-1 silencing transcription factor (REST) on neurons with Alzheimer’s Disease (AD), despite REST working as a master repressor of neuronal fate and being aberrantly upregulated in AD. To study REST, we used a model of 2D neural progenitor cell (NPC) cultures and inhibited REST with small molecule X5050 to elucidate its mechanism in relation to Alzheimer’s Disease. It was found that between 0, 1, 10, and 100 μM treatments of X5050 in AD neuron cultures, 1 μM was the optimal dosage for promoting the expression of neuronal genes, resulting in an average 44% increase of expression in neuronal genes targeted by REST compared to the 0 μM baseline. From this, we conclude that REST signaling is an important factor in regulating the expression of neuronal genes in early-onset Alzheimer’s disease neurons. Future work will target additional investigation of the downstream effects of REST manipulation on gene expression and translation.