PRNP and proteostasis deficiencies: However, the occurrence of aggregate “strains”, and the emerging implications of cofactor-dependent conformers for other proteopathies, in addition to the observance of misfolded proteins in the (seeming) absence of clinical signs in the human population, certainly suggests that misfolded proteins other than PrP prions may populate a spectrum of self-propagating states that may differ in their pathogenic outcomes.