Neurotransmitter release is governed by the formation of presynaptic SNARE complexes, a process tightly controlled to meet the unique regulatory requirements of a synapse. The SNARE complex proteins are maintained by accessory proteins, such as syntaxin-1 by Munc18-1. In addition to its role in chaperoning syntaxin-1, Munc18-1 is also involved directly in SNARE complex formation, and in its absence, neurotransmis-sion is abolished. Furthermore, mutations in Munc18-1 are linked to various severe ear-ly epileptic encephalopathies and neurodevelopmental disorders. In this thesis, we explore how the dysfunction seen in Munc18-1 encephalopa-thies may be alleviated, as there are currently no targeted therapies for these syndromes, and further investigate the mechanisms behind the neuronal dysfunction seen in the ab-sence of Munc18-1. Previous work has shown that human disease-linked missense mu-tations in Munc18-1 cause protein instability and aggregation, and the reduction in func-tional Munc18-1 protein leads to disease. We therefore hypothesized that stabilizing functional Munc18-1 can reduce these deficits and sought to identify Munc18-1 specific pharmacological chaperones. Through an in silico screen and in vitro validation experi-ments, we identified two such small molecules that bind to different sites on the Munc18-1 protein. These two chaperones boosted protein levels of WT Munc18-1 and two Munc18-1 mutants and ameliorated the synaptic deficits caused by mutant Munc18-1, both in vitro and in a C. elegans model of disease. Furthermore, we investigated the non-synaptic dysfunction seen in Munc18-1 knockout neurons to identify cellular pathways that may explain the non-epileptic symp-toms in affected patients. We find that in the case of Munc18-1 loss, its cognate SNARE partner, syntaxin-1, is retained in the Golgi apparatus and binds the Golgi SNARE syn-taxin-5, with which it normally does not interact. As a consequence, syntaxin-5 protein levels and syntaxin-5 containing SNARE complex levels are reduced. This is accompa-nied by a condensed Golgi phenotype. In addition, we find changes in synaptic proteins and neuronal markers in Munc18-1 knockout and mutant neurons and identify that syn-apses likely degenerate first with Munc18-1 loss, possibly due to Golgi dysfunction. These results not only further characterize the molecular mechanisms underlying Munc18-1 linked encephalopathies, but also introduce the first targeted treatment strate-gy for these devastating diseases.