Since HD pathology has multiple intersections with the impairment in peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), a transcriptional master co-regulator of mitochondrial biogenesis, metabolism, and antioxidant defenses, it is tempting to speculate that PGC-1α at the ER–mitochondria interface has an important role to play, just waiting to be explored. Here, PPARGC1A is linked to Huntington disease.