  Intrinsically disordered proteins (IDPs), such as amyloid polypeptide (IAPP),
beta-amyloid (A\b{eta}), and {\alpha}-synuclein are linked to the insurgence of
type 2 diabetes, Alzheimer's, and Parkinson's diseases, respectively. Common
molecular mechanisms have been explored to elucidate the toxicity pathway of
these proteins. For many years, the amyloid hypothesis was believed to explain
the toxicity. According to this hypothesis, the misfolding of these proteins
and the further aggregation into mature and insoluble fibrils rich in the
\b{eta}-sheet lead to cell death. However, this theory fails to explain much of
the experimental evidence, which led to the hypothesis of soluble
small-oligomer toxicity and pore-like activity. Recently, the lipid-chaperone
model was proposed to explain the effect of lipid compositions on IDPs toxicity
in vitro. In this work, we summarize the different toxicity models and discuss
the possible relevance of the lipid-chaperone model in a biological context,
such as protein overexpression and lipid oxidation. Furthermore, we briefly
explore how the model can be incorporated into the framework that explains IDPs
toxicity, such as fibril formation and secondary nucleation.
