The transcription factor nuclear factor kappa-B (NFxcexbaB) is a key regulator of pro-inflammatory and pro-proliferative processes. Accordingly, uncontrolled NFxcexbaB activity may contribute to the development of severe diseases when the regulatory system is impaired. Since NFxcexbaB can be triggered by a huge variety of inflammatory, pro-and anti-apoptotic stimuli, its activation underlies a complex and tightly regulated signaling network that also includes multi-layered negative feedback mechanisms. Detailed understanding of this complex signaling network is mandatory to identify sensitive parameters that may serve as targets for therapeutic interventions. While many details about canonical and non-canonical NFxcexbaB activation have been investigated, less is known about cellular IxcexbaBxcexb1 pools that may tune the cellular NFxcexbaB levels. IxcexbaBxcexb1 has so far exclusively been described to exist in two different forms within the cell: stably bound to NFxcexbaB or, very transiently, as unbound protein. We created a detailed mathematical model to quantitatively capture and analyze the time-resolved network behavior. By iterative refinement with numerous biological experiments, we yielded a highly identifiable model with superior predictive power which led to the hypothesis of an NFxcexbaB-lacking IxcexbaBxcexb1 complex that contains stabilizing IKK subunits. We provide evidence that other but canonical pathways exist that may affect the cellular IxcexbaBxcexb1 status. This additional IxcexbaBxcexb1:IKKxcexb3 complex revealed may serve as storage for the inhibitor to antagonize undesired NFxcexbaB activation under physiological and pathophysiological conditions. 