NHLRC3 (NHL repeat containing 3) is an E3 ubiquitin ligase involved in proteasome-mediated protein degradation through polyubiquitination, with broader roles in immune regulation and disease susceptibility. Functionally, NHLRC3 contains NHL repeat domains and possesses ubiquitin protein ligase activity, localizing to azurophil granules and extracellular regions, suggesting involvement in neutrophil biology and immune responses [GO Annotations]. Recent evidence demonstrates NHLRC3's clinical significance in multiple contexts: it was identified as part of a seven-gene prognostic model for gastric adenocarcinoma, where elevated expression associated with immune cell infiltration and worse treatment outcomes 1. In lentiviral vector engineering, NHLRC3 knockout enhanced viral production approximately 6.53-fold in combination with other gene knockouts, indicating its role in restricting viral packaging 2. NHLRC3 emerged as a candidate gene in genetic predisposition to brucellosis in goats, linking it to immune response regulation against bacterial infections 3. In rectal cancer, NHLRC3 protein levels predicted unfavorable neoadjuvant chemoradiotherapy response 4. These findings suggest NHLRC3 functions in immune surveillance, potentially through regulating protein degradation pathways critical for immune cell function and pathogen recognition.