Abstract: The cellular prion protein (PrPC), a cell surface glycoprotein of 209 amino acids, has been considerably studied over the decades mainly due to its critical involvement in transmissible spongiform encephalopathies, or prion diseases. Indeed, it is the misfolding and aggregation of PrPC into pathological assemblies - named PrPSc – that constitute prions, the agents causing these unusual neurodegenerative diseases affecting humans and animals (Prusiner, 1982). Furthermore, increasing evidence support its relevance also in other neurodegenerative diseases (NDDs), such as Alzheimer’s and Parkinson’s diseases (Corbett et al., 2020).