Since ER–mitochondria associations at the MAM (lipid raft-like microdomains) are central in correct folding as well as distribution of mature proteins to the appropriate locations within the cell, it is tempting to speculate that the misfolding and aggregation of the various mutated proteins (e.g., mutant huntingtin in HD, α-synuclein in PD, etc.)starts at the MAM. This evidence concerns the gene HTT and Huntington disease.