No physiological activating ligand is known for this orphan receptor, but 4-hydroxytamoxifen and diethylstilbestrol act as inverse agonists and deactivate ESRRG.

There is evidence that bisphenol A functions as a xenoestrogen by binding strongly to ERR-γ.

[8] BPA as well as its nitrated and chlorinated metabolites seems to binds strongly to ERR-γ (dissociation constant = 5.5 nM), but not to the estrogen receptor (ER).,[8][10] BPA binding to ERR-γ preserves its basal constitutive activity.

[8] It can also protect it from deactivation from the selective estrogen receptor modulator 4-hydroxytamoxifen.

[8] Different expression of ERR-γ in different parts of the body may account for variations in bisphenol A effects.