Understanding the endocytic itinerary of PrPC is fundamental, since data in the literature indicate that both general inhibition of endocytosis [8], [12] and/or a direct modification of the internalization route of PrPC, by replacing the GPI anchor with a transmembrane sequence containing a coated pits localization motif [9], affect both the infection and the conversion processes [3], [44]. Here, PRNP is linked to infection.