Leucine-rich repeat flightless-interacting protein 1 (LRRFIP1)

Leucine-rich repeat flightless-interacting protein 1 (LRRFIP1) is a multifunctional transcriptional regulator that binds to both DNA and RNA with high specificity. It acts primarily as a transcriptional repressor, especially at GC-rich promoter regions, and negatively regulates the expression of growth factor and receptor genes such as EGFR and PDGFA[1][2]. LRRFIP1 also interacts with proteins involved in cytoskeletal remodeling, such as Flightless-1, and plays a role in cell migration and morphology[1]. In signaling pathways, LRRFIP1 co-stimulates β-catenin/Wnt and TLR/MyD88/NF-κB-mediated immune responses, affecting both inflammation and immune defense[1][2]. Dysregulation of LRRFIP1 contributes to the development and progression of several diseases, notably cancer (where it promotes growth, EMT, and drug resistance), autoimmune conditions, obesity, and inflammatory states[1][6]. LRRFIP1's expression acts as a biomarker in some cancers, and it may mediate chemosensitivity by modifying membrane transporter trafficking and cytoskeletal organization[1]. Its structural features include an N-terminal helix, coiled-coil domain, and a C-terminal nucleic acid binding motif[1][5].

Other names

GCF2TRIPFLAP-1FLIIAP1HUFI-1GC-binding factor 2TAR RNA-interacting proteinFLAP1GCF-2NEDD8-conjugating enzyme (sometimes referenced, but not canonical)leucine-rich repeat flightless-interacting protein 1

Modulates drug efflux by altering membrane transporter localization (e.g., MRP1 internalization affecting therapeutic efficacy of doxorubicin and vincristine). Transcriptional repression of growth factor/receptor genes (e.g., EGFR, PDGFA). Regulates immune gene transcription via Wnt and TLR/MyD88/NF-κB pathways.