In hopes of discovering new routes of therapeutic interventions, the Schultz laboratory studies protein homeostasis and the underlying genetic causes of rare inherited childhood diseases. His laboratory leverages induced pluripotent stem cells (iPSCs), iPSC derived neurons/hepatocytes, and mouse models to study and modulate protein folding/degradation in brain and liver. Dr. Schultz’s research primarily focuses on Niemann-Pick type C disease, a rare childhood neurovisceral lysosomal storage disorder resulting from impaired cholesterol trafficking. Niemann-Pick C is commonly caused by loss-of-function mutations in the NPC1 gene (95% of cases). NPC1 encodes NPC intracellular cholesterol transporter 1 (NPC1), a multipass transmembrane glycoprotein required for exporting unesterified cholesterol from late endosomes and lysosomes. His research group has found that some NPC1 mutants misfold in the endoplasmic reticulum (ER) and are rapidly degraded by the proteasome and through ER-autophagy, a specific form of autophagy that removes misfolded ER proteins. Importantly, many of the NPC1 mutants are functional if trafficked to the lysosome, i.e., mutant-NPC1 can export unesterified cholesterol out of the lysosome. This observation has spurred my interest in acquiring a comprehensive understanding of the process of NPC1 degradation, with the ultimate goal of using this knowledge to develop proteostasis (protein homeostasis) modulators to restore the function of the mutated versions of NPC1.