An international team has assessed the impact of 45 natural variants of the prion protein (PrP) in cervids on its thermal stability, structural flexibility and propensity for spontaneous misfolding. Using the Protein Misfolding Shaking Amplification (PMSA) technique, the researchers demonstrated that most of these variants can generate infectious prions, regardless of their thermal stability. This finding reveals the great versatility of PrP in cervids to adopt pathological conformations, with relevant implications in the context of cases of chronic wasting disease (CWD) detected in Europe that differ from North American strains. The study highlights the need to continue monitoring the diversity of PrP variants and their zoonotic potential.