Recent evidence suggests a role for TNF superfamily member Tumor necrosis factor-like weak inducer of apoptosis (TWEAK, Apo3L, or TNFSF12) in both AKI and CKD, where it has been shown to regulate cell death, inflammation, and fibrosis through activation of the TWEAK receptor Fn14 and a variety of intracellular signaling pathways, including the transcription factor nuclear factor-kappa B (NF-κB) (4, 5) (Figure 1). The gene discussed is TNFSF12; the disease is acute kidney injury.