If we can consider mucus clearance as an engineering system consisting of actuators, sensors and mechanical linkages, then the electronic circuitry for power and control is the biochemical network. All of the feedback mechanisms flow through the biochemical networks. We need to couple the identified subsystems together through a biochemical network that controls ion flow and water movement across the cell membrane, regulates mucin secretion and controls cilia beating. The inputs to the feedback system are the sensing of ASL volume through biochemical sensing, and the sensing of ASL volume and rheology through mechanosensing. Underlying all of these is nucleotide metabolism. Biochemical network modeling has largely focused on intercellular networks. Our concern is with the parts of those networks that connect to the primary events that dictate the health of mucus clearance. We therefore start with nucleotide metabolism as it is transported across the cell membrane and the network in the extracellular environment. Remarkably, no network model for this system yet exists. Successively, we will expand our network model to include the biochemical control of ion and hence water secretion, mucin secretion and finally cilia beat cycle. Immediately, in the modeling of ion transport, we will address one of the genetic origins (the CFTR protein) of mucus stasis, and begin to understand one of the strongest predictors of mucus clearance efficacy, ASL volume and rheology through water transport. Beyond addressing the stability of the healthy system and its compromise in the absence of the CFTR channel, our biochemical model will be able to address therapeutic strategies such as nucleotide dosing in the ASL.