To provide brain protection and avoid off-target effects on breast, ERb ligands are being investigated.2 A menopause model showed that ligation of ERb on astrocytes improved cognitive testing performance and reduced hippocampal atrophy, while decreasing glial activation and synaptic loss.2 In MS models, ERb ligand treatment decreased microglial activation, reduced synaptic loss, and induced remyelination through binding to microglia and oligodendrocytes.4,5. The gene discussed is ESR2; the disease is hippocampal atrophy.