Besides playing a central role in fatal neurodegenerative maladies such as prion diseases (also known as transmissible spongiphorm encephalopathies), the prion protein (PrP) is currently one of the best studied models for disease-causing protein misfolding. PrP is in fact the first system in which a protein was observed to exist as at least two radically different conformers, each associated to completely different functions. The cellular form of the prion protein (PrP^C) is a cell-surface glycosylphosphatidylinositol-anchored glycopolypeptide (GPI) expressed in many mammalian species. After misfolding, PrP^C can convert to a disease-causing isoform denoted PrP^Sc, so far the only known disease agent in prion maladies. The pre-pro-protein is comprised of 253 amino acids in humans (22 amino acids within the signal sequence in the N-terminal, and 23 amino acids as C-terminal GPI-anchoring signal). The PrP^C N-terminal features five repeated sequences binding copper and, to a lesser extent, other metal ions.

The physiological function of PrP^C has not been fully clarified yet. This work aims at discussing recent discoveries in order to delineate a possible role for PrP in neuronal differentiation and polarization as well as synaptic plasticity.