Converging molecular and electrophysiological data indicate that ER-β and GPER1 activation enhances BDNF transcription, facilitates hippocampal long-term potentiation (LTP), and calibrates monoaminergic tone across dopaminergic and serotonergic (5-HT1A) circuits—systems frequently disrupted in treatment-resistant BD (TR-BD) (13–15, 17, 18). Here, ESR2 is linked to Behcet disease.