The Trem2‐Igf1 signaling pathway underpins microglial metabolism under cerebral ischemia‐reperfusion circumstances, in which overexpression of Igf1 alone or supplementation of cyclocreatine could enhance microglial oxidative phosphorylation levels, and consequently promote microglial proliferation and exert neuroprotective properties, even in the absence of Trem2. The gene discussed is IGF1; the disease is brain ischemia.