In the present study, we unveil a novel mechanistic link between tumor necrosis factor-like weak inducer of apoptosis (TWEAK) signaling and Human antigen R (HuR)-driven metabolic alterations in lupus nephritis (LN), a progressive renal disorder characterized by mesangial cells (MCs) hyperproliferation and glomerular dysfunction. This evidence concerns the gene TNFSF12 and lobular neoplasia.