Our previous studies have shown that: 1) microglial interferon regulatory factor 5 (IRF5) and IRF4 regulate neuroinflammation in young [21] and aged mice [22]; 2) X chromosomal complement contributes to stroke sensitivity in aged animals [23]; and 3) the X escapee genes Kdm6a and Kdm5c were involved in IRF5/4 expression and neuroinflammation after stroke [24]. Here, IRF5 is linked to stroke disorder.