Cellular prion protein (PrP^C) is a membrane bound protein that undergoes several post translational modifications. It can exert pleiotropic functions either in physiological and pathological conditions. The disease-causing isoform of the prion protein, called PrP^Sc, acts as corruptive seed able to establish a process of misfolding and aggregation of further PrP^Sc molecules. Therefore, PrP^C acts as substrate for PrP^Sc formation and as receptor to convey neurotoxic functions typical of other prion-like proteins involved in several neurodegenerative conditions.

PrP^C is transported from the outer leaflet of the cellular membrane to the intracellular compartments through several endocytic pathways, including clathrin-dependent and independent mechanisms and interactions with different adaptor proteins. During prion infection, the pathological counterpart PrP^Sc, can be uptaken by the cells with mechanisms partially overlapping the ones of the physiological form, PrP^C.

The intercellular routing of both prion protein isoforms involves the release through vesicles and tunneling nanotubes. From the extracellular milieu, PrP^C and PrP^Sc can be uptaken by adjacent cells, thus exerting physiological and pathological functions.