In summary, our data revealed that LY3000328 could alleviate the neuroinflammation response, decrease Aβ deposition, and rescue the learning and memory deficits in APP/PS1 mice via the CX3CL1‐CX3CR1 axis and JAK2‐STAT3 pathway, suggesting that CTSS has great potential for use as an effective target for treating AD. The gene discussed is STAT3; the disease is Alzheimer disease.