Regenerating islet-derived 3 (REG3) proteins belong to the family of C-type lectins (Cash HL et al. 2006a,b; Lehotzky RE et al. 2010). REG3A and REG3G are induced and expressed in the intestine where they function as antibacterial peptides by targeting the peptidoglycan moieties of bacteria. NMR spectroscopy revealed that human REG3A lectin recognized the peptidoglycan carbohydrate backbone in a calcium-independent manner via a conserved “EPN” motif that is critical for bacterial killing (Lehotzky RE et al. 2010). The antibacterial activities of REG3 proteins are restricted to Gram-positive bacteria and are tightly controlled by an inhibitory N-terminal pro-segment that is removed by trypsin in vivo (Cash HL et al. 2006; Mukherjee S et al. 2009; Medveczky P et al. 2009).