Adding HOIP to the clinical model increased the AUC from 0.846 to 0.907 and further improved model calibration and clinical net benefit.<h4>Conclusion</h4>Peripheral blood HOIP and OTULIN may serve as candidate biomarkers associated with stroke severity in AIS, while HOIP may provide additional prognostic information for functional outcome. Here, RNF31 is linked to stroke disorder.