In vitro studies in lupus serum-induced CVECs and in vivo studies in PIL mice further corroborated SQDHD downregulation of elevated levels of adhesion molecules, potentially through inhibition of JAK1-STAT3 signaling.<h4>Conclusions</h4>SQDHD may exert neuroprotective effects in NPSLE by inhibiting the activation of CVECs through blocking the JAK1-STAT3 signaling pathway, thereby suggesting its potential as a promising therapeutic strategy for NPSLE. The gene discussed is STAT3; the disease is systemic lupus erythematosus.