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Introduction: Olfactory impairment is one of the earliest symptoms in neurodegenerative disorders that has also been documented in Niemann-Pick disease type C1 (NPC1). NPC1 is a very rare, neurovisceral lipid storage disorder, characterized by a deficiency of <i>Npc1</i> gene function that leads to progressive neurodegeneration. Here, we compared the pathologic effect of defective <i>Npc1</i> gene on the vomeronasal neuroepithelium (VNE) with that of the olfactory epithelium (OE) in an NPC1 mouse model. Methods: Proliferation in the VNE and OE was assessed by applying a bromodeoxyuridine (BrdU) protocol. We further compared the immunoreactivities of anti-olfactory marker protein (OMP), and the lysosomal marker cathepsin-D in both epithelia. To investigate if degenerative effects of both olfactory systems can be prevented or reversed, some animals were treated with a combination of miglustat/allopregnanolone/2-hydroxypropyl-cyclodextrin (HP&#946;CD), or a monotherapy with HP&#946;CD alone. Results: Using BrdU to label dividing cells of the VNE, we detected a proliferation increase of 215% &#177; 12% in <i>Npc1</i>&#8722;/&#8722; mice, and 270% &#177; 10% in combination- treated <i>Npc1</i>&#8722;/&#8722; animals. The monotherapy with HP&#946;CD led to an increase of 261% &#177; 10.5% compared to sham-treated <i>Npc1</i>&#8722;/&#8722; mice. Similar to the OE, we assessed the high regenerative potential of vomeronasal progenitor cells. OMP reactivity in the VNE of <i>Npc1</i>&#8722;/&#8722; mice was not affected, in contrast to that observed in the OE. Concomitantly, cathepsin-D reactivity in the VNE was virtually absent. <b>Conclusion:</b> Vomeronasal receptor neurons are less susceptible against NPC1 pathology than olfactory receptor neurons. Compared to control mice, however, the VNE of <i>Npc1</i>^{&#8722;/&#8722;} mice displays an increased neuroregenerative potential, indicating compensatory cell renewal.