While this might reflect a protective feature of blocking toxic oligomers extracellularly in some conditions (e.g., in AD), the consequences of PrP shedding might be more ambivalent in prion diseases (where ‘anchorless misfolded PrP entities’ potentially involved in disease spreading and transmission, and maybe representing bona fide ‘prions’ are generated by ADAM10). Here, PRNP is linked to prion disease.