Fibroblast growth factor-inducible 14 receptor (Fn14)

Fibroblast growth factor-inducible 14 receptor (Fn14), also known as the TWEAK receptor (TWEAKR) and encoded by the TNFRSF12A gene, is the smallest member of the tumor necrosis factor receptor superfamily[7]. Fn14 acts as the primary signaling receptor for the cytokine TWEAK (tumor necrosis factor-like weak inducer of apoptosis)[3][5][7][8]. Upon ligand binding, Fn14 triggers multiple intracellular pathways—including NF-κB, MAPK, and PI3K/Akt—modulating cellular processes such as proliferation, migration, differentiation, apoptosis, and inflammation[3][5][9]. Fn14 expression is typically low in normal tissues but markedly upregulated in response to injury, inflammation, and malignancy[5][7][8]. The TWEAK–Fn14 axis is implicated in pathological processes such as cancer progression, neurodegeneration, cardiovascular diseases, and fibrotic disorders, making it an important therapeutic target[3][5][7][8][9]. Antibody drugs such as RG7212 are under investigation to modulate this signaling pathway in inflammatory diseases and cancer[8]. While research into the TWEAK–Fn14 axis is ongoing, safety concerns center on the potential for disturbing normal repair mechanisms and immune regulation[5].

Other names

Tumor necrosis factor receptor superfamily member 12ATNFRSF12ATWEAK receptorTWEAKRCD266Fibroblast growth factor inducible immediate early response protein 14

Inhibition of TWEAK–Fn14 interaction to suppress NF-κB and other proinflammatory signaling pathways; Antibody-mediated blockade preventing Fn14-mediated cellular responses