NLRC3 is a negative regulator of innate immunity that attenuates excessive inflammatory responses through multiple signaling pathways. Primary functions include inhibition of Toll-like receptor (TLR) and STING-mediated DNA sensing pathways in response to pathogens 1, with mechanistic involvement in TRAF6 ubiquitination modulation and suppression of NF-κB activation 12. NLRC3 also inhibits the PI3K-AKT-mTOR pathway by disrupting interactions between phosphatidylinositol 3-kinase regulatory and catalytic subunits, controlling epithelial cell proliferation 2. Additionally, NLRC3 prevents NLRP3 inflammasome formation and IL-1β maturation 2. Disease relevance is substantial: NLRC3 deficiency promotes hypoxia-induced pulmonary hypertension through IKK/NF-κB p65/HIF-1α pathway activation 3, and impairs regulatory T cell function in pulmonary hypertension associated with left heart disease via IL-18/IRF3/NF-κB signaling 4. NLRC3 knockdown enhances colon cancer cell proliferation and invasion 5. Conversely, systemic sclerosis pathogenesis involves suppression of NLRC3, leading to excessive Th9 cell differentiation 6. Clinically, NLRC3 represents a therapeutic target: NLRC3 inhibition augments anti-tumor immunity via cGAS-STING pathway enhancement 7, while NLRC3 restoration could ameliorate immunomodulatory and vascular remodeling diseases.