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). Here, TNFRSF12A is linked to chronic kidney disease.