Our data show that (a) SBSPON is markedly downregulated in human bladder cancer, (b) SBSPON acts as a potential tumor suppressor in vivo and in vitro, (c) SBSPON is a novel HSPA5 binding glycoprotein, (d) SBSPON inhibits bladder cancer process through HSPA5/AKT/GSK-3β signal pathway, (e) SBSPON inhibits cisplatin resistance of bladder cancer cells by attenuating HSPA5's apoptotic inhibitory effects through physically interacting with HSPA5. Here, GSK3B is linked to urinary bladder carcinoma.