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In China, Procambarus clarkii has grown to be one of the most important cultivated crustacean species due to its excellent resistance ability against viral and bacterial infection. However, this broad-spectrum mechanism of disease resistance is less well known. In this study, a new LGBP known as Pc LGBP was cloned and described. Its full-length cDNA is 1200 bp with an open reading frame (ORF) of 1086 bp, encoding a 361 amino acid polypeptide. The transcripts of Pc LGBP were widely dispersed in P. clarkii tissues, with particularly elevated expression levels in hemocytes. Furthermore, Aeromonas hydrophila and white spot syndrome virus (WSSV) challenge dramatically increased its mRNA expression in hemocytes and gills. The purified recombinant Pc LGBP protein could bind to different kinds of pathogenic microorganisms, demonstrating a broad-spectrum pathogen recognition ability. Besides, Pc LGBP knockdown by RNA interference and r Pc LGBP injection experiments confirmed that the protein could apparently accelerate the bacterial clearance and inhibit the WSSV proliferation in vivo , thus increase the survival rate of A. hydrophila or WSSV infected P. clarkii. Further studies revealed that silencing of Pc LGBP resulted in inactivation of prophenoloxidase (proPO) system, decreased the expression levels of Toll/IMD pathway components, as well as some antimicrobial peptides (AMPs). Taken together, Pc LGBP may protect P. clarkii from diverse invading pathogens through activating the proPO system, NF-κB pathway and the expression of AMPs. These findings would contribute to the exploration of the crustacean immunity regulatory mechanisms and hold potential for the disease resistance breeding of P. clarkii. • A novel member of LGBP family named Pc LGBP was identified in Procambarus clarkii. • Pc LGBP was involved in both anti-bacterial and anti-viral immune response. • Pc LGBP exhibited broad-spectrum resistance ability in vivo. • Pc LGBP participate in the activation of the proPO system and NF-κB pathway. [ABSTRACT FROM AUTHOR]