NLRP12 in cancer: a context-dependent regulator of tumor progression, immunity, and metabolism

NLRP12, a member of the NOD-like receptor family, has traditionally been regarded as an inflammasome-associated regulator of inflammatory signaling. However, accumulating evidence indicates that its role in cancer extends far beyond classical inflammasome biology. Recent studies show that NLRP12 exerts highly context-dependent functions across malignancies, acting as either a tumor suppressor or a tumor promoter depending on tumor type, cellular source, and dominant signaling environment. In inflammation-associated and epithelial malignancies such as colorectal cancer, hepatocellular carcinoma, and triple-negative breast cancer, NLRP12 suppresses tumor progression by restraining noncanonical NF-κB, Wnt/β-catenin, JNK, or canonical NF-κB signaling. In contrast, in gastric cancer, ovarian cancer, glioma, and macrophage-rich tumor ecosystems, NLRP12 has been linked to glycolytic remodeling, lactate-associated epigenetic adaptation, aggressive clinicopathological features, and immune suppression. Mechanistically, NLRP12 has emerged as a multifunctional signaling regulator that connects inflammatory control with oncogenic pathway modulation, metabolic rewiring, tumor-associated macrophage polarization, and PANoptosis-related stress responses. These findings position NLRP12 at the crossroads of tumor progression, immunity, metabolism, and inflammatory cell death. In this review, we summarize the molecular and functional landscape of NLRP12 in cancer, with emphasis on its dual roles in tumor biology, its context-specific mechanisms, and its potential clinical relevance as a biomarker and therapeutic reference point. A deeper cell-resolved and mechanism-oriented understanding of NLRP12 may help redefine this molecule from a conventional innate immune regulator to a context-dependent organizer of tumor ecosystems.