Taking into account the relevance of the smell sense in the early diagnosis of neurodegenerative diseases, we have analyzed the expression profile of the dark proteome across public proteomic and transcriptomic data derived from primary olfactory areas such as olfactory bulb (OB) and cleft mucus as well as from specific brain/OB cell linages. In this study, we have used an experimental workflow combining neuropathological diagnosis, co-regulation maps, physical and functional interaction data, transgenic models, intracellular and extracellular proteomics and immunohistochemical and biochemical approaches to partially decipher the UPE1 PITHD1 function in olfactory metabolism.