Here we review emerging evidence that APP/Aβ, α-syn, and mHtt may contain “cryptic” sequences that mimic the classic N-terminal targeting information of mitochondrial proteins to interact with mitochondrial import complexes, the implications this may have for the role of mitochondrial dysfunction in neurodegeneration, and how such insights could inform the development of novel therapeutic strategies for AD, PD, and HD. This evidence concerns the gene APP and Huntington disease.