Neurofibromatosis 1 (NF1) is a hereditary autosomal dominant disorder affecting 1 in 3500 individuals. It presents with skin abnormalities, Lisch nodules, and neurofibromas. Patients often exhibit macrocephaly, short stature, learning disabilities, and attention deficits. Children and adults with NF1 are also at increased risk for sleep disturbances. The human NF1 gene (17q11.2) encodes neurofibromin, a 2818-amino-acid protein expressed in various nervous system cells throughout life. Nf1 best-understood and evolutionarily conserved role is as a GTPase Activating Protein (GAP) for Ras, which reduces Ras biological activity. The GRD domain comprises about 10% of the protein (229 amino acids), while the functions of other protein regions remain largely unidentified. Mutations outside the GAP domain are known to precipitate pathological effects in patients. To understand the disturbed mechanisms underlying sleep defects we use the genetic power of Drosophila (ortholog of the human, dNf1), to investigate locomotor activity and a sleep-like state in mutants and patient mimicking point mutations. Using the Trikinetics automatic monitoring system, we report circadian and several sleep deficits, which also present mutation specificity. We are investigating the neuronal circuitry that drives these behaviors and is affected by dNf1 mutations and the affected molecular pathways therein. Our data thus far reveal complex regulation of activity and sleep by dNf1, probably mediated by distinct neurons in the fly central nervous system. This aligns with the observed diversity of patient phenotypes, especially when considering that various mutations can lead to distinct tissue-specific consequences, contingent upon the specific Nf1 domain that is affected.