Estrogen receptor α, or ERα, is believed to play a central role in controlling inflammation. Research suggests that ERα does that by regulating anti-inflammatory signaling in the microglia, the only immune cells that reside in the brain. Now, a new study confirms ERα’s beneficial role in the brains of mice. The work explored one mechanism believed to prime ERα to fight inflammation, the attachment of a phosphoryl group to a specific amino acid in ERα’s structure -- a process known as “phosphorylation”. To test that mechanism, researchers blocked the phosphorylation of ERα in microglia from mice. That absence, it turned out, compromised the cells’ defenses against inflammation – leaving mice vulnerable to negative effects. For example, some mice with blocked ERα phosphorylation were obese and showed weakened motor skills. Further study could help explain how phosphorylated ERα regulates brain immunity and inflammation in brain diseases.