Our results showing that cholesterol binds directly and specifically to the purified ligand binding domain of ERRα, with a dissociation constant of approximately 210 nM, and increases transcriptional activity of ERRα in a PGC-1α-dependent manner in both ER-positive and triple-negative breast cancer cells, indicate that cholesterol acts as an endogenous agonist of ERRα-PGC-1α signaling in these cells. Here, ESR1 is linked to triple-negative breast carcinoma.