Twenty-five SLE patients were enrolled and divided into the responder group and non-responder group based on the SLE Response Index 4 to identify key proteins, metabolites, and mechanisms associated with treatment response.<h4>Results</h4>Proteomics results revealed XPNPEP3, SRSF5, SRSF6, WARS1, IDH1, and ITLN1 as protein biomarkers correlated with Telitacicept efficacy in SLE patients. Here, SRSF5 is linked to systemic lupus erythematosus.