As TNF signaling plays a crucial pathogenic role in obesity-associated hepatic inflammation and hepatocarcinogenesis (10), the constitutively elevated p65 phosphorylation NLRC5-deficient livers also warrants further investigations into possible regulatory functions of NLRC5 on NF-κB activation and TNF production under milder but chronic inflammatory conditions such as the one associated with diet-induced fatty liver disease and HCC development. Here, NLRC5 is linked to obesity due to melanocortin 4 receptor deficiency.