Guanylate-binding protein 1 (GBP-1) is a member of the GBP family whose members are GTPases induced in response to interferon-λ (IFN-λ), with seven highly homologous members in humans, termed HuGBP-1 to HuGBP-7. GBP-1 expression is induced by type1 and type2 interferons, including IFN-λ and also by interleukin-1β (IL-1β), IL-1α, and tumor necrosis factor-α (TNF-α). GBP-1 is key to the protective immunity against microbial and viral pathogens. GBP-1 was only secreted from endothelial cells. Secretion occurred without the presence of a leader peptide. Secretion procession is a nonclassical, likely ABC transporter-dependent, pathway and independent of GBP-1 GTPase activity and isoprenylation, and did not require additional interferon-λ-induced factors. Clinically most important was the detection of significantly increased GBP-1 concentrations in the cerebrospinal fluid of patients with bacterial meningitis as compared to control patients.