Besides the search of mutations in PRNP, which represent the main diagnostic tool for familial prion disease, electroencephalographic findings, brain-derived cerebrospinal fluid (CSF) protein assays serving as surrogate markers for neuronal damage, and diffusion-weighted magnetic resonance imaging (DW-MRI), have provided the primary support for the clinical diagnosis of prion disease in the past 20 years. Here, PRNP is linked to prion disease.