Mitochondrial and ER proteins (e.g., PERK, IRE1, eiF2α, BiP, CHOP, GRP78, XBP1, ATF6, and ATF4) are known to be altered in diverse neurodegenerative diseases, and may be similarly aberrant in cardiac tissue, leading to protein aggregation and cardiomyopathy. This evidence concerns the gene HSPA5 and neurodegenerative disease.