Multiple polymorphs of αSyn fibrils have been observed in both patient samples and in vitro studies using recombinant monomer . The structural variation of fibrils assembled in vitro is dictated by the solution conditions of the aggregation assay, including pH, salt concentration, incubation temperature, or shaking . Conversely, the diversity of fibril polymorphs isolated ex vivo may be attributed to the unique cellular environments characteristic for each disease (similarly to what has been observed for the tau protein ). These include dopaminergic neurons in PD and oligodendrocytic glial cells in different brain regions in MSA . This is supported by the finding of unknown electron densities in the structures of both disease-related αSyn polymorphs, indicating a cell specific "aggregation cofactor" whose absence explains the inability to replicate these structures in vitro using seeded experiments . While it is plausible for different fibril polymorphs to nucleate in a cellular environment, disease-specific polymorph evidence suggests that only one polymorph emerges as the dominant competitor, propagating itself due to higher stability, faster kinetics, or better compatibility with the cellular environment, including ligands or post-translational modifications (PTMs).