NLRC5 is a NOD-like receptor (NLR) that functions as a critical regulator of innate immunity and antigen presentation. Primarily, NLRC5 acts as a master transcriptional regulator that promotes MHC class I gene expression 1, while also governing interferon signaling pathways and inflammatory responses 2. Mechanistically, NLRC5 senses pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to drive PANoptosis, a form of inflammatory cell death, through interaction with other NLR family members and components of the PANoptosome complex 3. NLRC5 expression is regulated by TLR signaling and NAD+ levels, controlling ROS production and cell death outcomes 3. In disease contexts, NLRC5 plays protective anti-inflammatory roles: it suppresses endometriosis development through inhibition of ERβ-mediated inflammatory responses 4, and its upregulation enhances antitumor immunity by promoting MHC-I-mediated antigen presentation and CD8+ T cell infiltration 256. Clinically, NLRC5 expression correlates with improved survival in melanoma and lung cancer patients 27. NLRC5 represents a potential therapeutic target for enhancing cancer immunotherapy and treating inflammatory diseases, though NLRC5-deficient mice show protection in hemolytic models, suggesting context-dependent therapeutic applications 3.