LAUSR

α‐Synuclein (α‐Syn) is an intrinsically disordered protein in solution whose fibrillar aggregates are the hallmark of Parkinson's disease (PD). Although the specific function of α‐Syn is still unclear, its high structural plasticity is key for the interactions of α‐Syn with biological membranes. Recently, it has been observed that α‐Syn is able to form high‐density lipoprotein‐like (HDL‐like) particles that are reminiscent of self‐assembling phospholipid bilayer nanodiscs. Here, we extended our preparation method for the production of α‐Syn lipoprotein particles to the β‐ and γ‐Syn variants, and the PD‐related familial α‐Syn mutants. We show that all human Syns can form stable and homogeneous populations of HDL‐like particles with distinct morphologies. Our results characterize the impact of the individual Syns on the formation capacity of these particles and indicate that Syn HDL‐like particles are neither causing toxicity nor a toxicity‐related loss of α‐Syn in PD.