NLRP12 as a Regulator of Inflammation: Insights into the Correlation with Autoinflammatory Disorders.

Background: Dysregulation of the innate immune system is a key feature of autoinflammatory disorders, characterized by recurrent or chronic inflammation in the absence of high-titer autoantibodies and antigen-specific T cells. Among regulators of innate immunity, NLRP12 has emerged as an important modulator of inflammatory signaling pathways. As a member of the nucleotide-binding oligomerization domain-like receptor (NLR) family, NLRP12 negatively regulates nuclear factor (NF)-κB activity and contributes to immune homeostasis. However, the clinical significance of NLRP12 variants and their association with disease phenotypes remain incompletely understood. This study aims to summarize current knowledge on the molecular role of NLRP12 and its involvement in autoinflammatory manifestations. Methods: A narrative review of the literature on NLRP12's molecular functions and role in autoinflammatory diseases was performed. In addition, a cohort of 20 patients with recurrent fevers carrying NLRP12 variants was analyzed from a clinical perspective, evaluating genetic findings and clinical features. Results: Available evidence indicates that NLRP12 regulates inflammatory signaling, particularly through modulation of NF-κB activity. Variants in the NLRP12 gene have been associated with a spectrum of autoinflammatory phenotypes, ranging from periodic fever syndromes to broader systemic inflammatory manifestations. Clinical evaluation of the cohort confirmed the heterogeneity of disease presentations among individuals carrying NLRP12 variants. Conclusions: NLRP12 plays an important role in the regulation of innate immune responses and may contribute to autoinflammatory phenotypes. Integrating molecular data with clinical observations may improve the understanding of NLRP12 variants and support more accurate diagnostic and therapeutic strategies.