Abstract Increased lymphocyte apoptosis has been suggested to contribute to the development of systemic lupus erythematosus (SLE), but the critical factors involved in the apoptotic pathways are still unknown. By long serial analysis of gene expression (LongSAGE) profiles and microarray analyses, a novel apoptosis-related gene BclG L expression was found significantly increased in peripheral blood CD4 + T cells of SLE patients, which was correlated with the enhanced CD4 + T cells apoptosis, anti-nuclear antibody (ANA) titer and proteinuria. In vitro, BclG L expression could be specially upregulated by SLE serum stimulation and positively correlated with induced CD4 + T cell apoptosis. Enforcing BclG L overexpression by lentivirus could directly enhance CD4 + T cell apoptosis, but these apoptosis-inducing effects could be partially inhibited by knockdown of BclG L expression. Collectively, these results indicate that increased BclG L expression may contribute to the aberrant CD4 + T cell apoptosis which causes an inappropriate immune response and impaired homeostasis in SLE.