LRRFIP2 (leucine-rich repeat Fli-I-interacting protein 2) functions as a dual signaling regulator in Wnt and Toll-like receptor (TLR) pathways. In Wnt signaling, LRRFIP2 acts as a positive regulator by interacting with Disheveled (DVL3) to stabilize β-catenin and activate LEF/TCF-dependent transcriptional activity 1. Expression of LRRFIP2 in Xenopus embryos induces double axis formation and Wnt target gene expression, while dominant negative forms suppress Wnt signaling 1. In TLR signaling, LRRFIP2 positively regulates NF-κB activity through dynamic interactions with MyD88, competing with negative regulators like FLII for MyD88 binding 2. LPS stimulation induces phosphorylation of LRRFIP2 at serine 202, which strengthens its interaction with MyD88 and modulates TLR4 signaling duration 3. LRRFIP2 also regulates NLRP3 inflammasome activity through interactions with F-actin and Flightless-I, dampening IL-1β production 4. Disease relevance includes involvement in gastric cancer metastasis through epithelial-mesenchymal isoform switching 5 and rare RAF1 fusions in melanoma 6. The protein demonstrates evolutionary conservation, with functional homologs identified in shrimp showing antimicrobial peptide regulation 7.