Cloned a novel Spätzle gene (LvSpz4) in Litopenaeus vannamei. Spaetzle domain of LvSpz4 activated the promoter of antibacterial peptide genes and WSSV ie1 gene in S2 cells. LvSpz4 was upregulated by Vibrio alginolyticus-, Staphylococcus aureus infection or lipopolysaccharide stimulation. Knocked-down expression of LvSpz4 caused a higher cumulative mortality upon V. alginolyticus infection for L. vanname. LvSpz4 was induced by unfolded protein response (UPR) in L. vannamei.