The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) elicits cellular responses by signaling through a receptor complex that includes the essential adaptor molecule RIP. One important consequence of signaling is activation of the transcription factor NF-kappaB, and failure to downregulate TNF-induced NF-kappaB transcriptional activity results in chronic inflammation and death. Internalization of the receptor complex plays an important regulatory role in TNF signaling.