Tobacco use is the leading preventable cause of death in the world. Nicotine, which is the addictive ingredient of tobacco, exerts its addictive effect through nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). Besides mediating nicotine addiction, nAChRs have been implicated in Alzheimer’s disease, Parkinson’s disease, learning and memory, autism, anxiety disorders, depression, cell motility and cellular adhesion. Lynx1 has recently been identified as a modulator of nAChRs and it functions in nicotinic receptor mediated learning and neurodegeneration. Lynx1 is a member of Ly6 superfamily of proteins (Ly6SF), which is a large protein family that consists of proteins with a characteristic three-finger topology. Lynx family consists of ~100 kDa proteins that function mainly in the nervous system through nicotinic receptor modulation. We have recently identified Lynx2 as another modulator of nicotinic receptor activity which is involved in fear and anxiety related behavior. Lynx3 is a novel member of this family that is expressed in high levels in lung epithelial cells that are specifically important in mechanical sensation. We plan to characterize the molecular function of Lynx3 and its association to lung disease through molecular biological, physiological and behavioral techniques. Our work plan can be grouped under the following headings: 1) Characterization of Lynx3 expression in lung respiratory epithelia and other sensory epithelia. 2) Functional characterization of Lynx3 in vitro through immünoprecipitation experiments and electrophysiology. 3) Physiological analysis of Lynx3 function through targeted-deletion of Lynx3 in mouse models. Our previous work and cited literature suggest that nicotinic acetylcholine receptors are involved in lung physiology, specifically nicotinic receptor associated cellular motility and cell adhesion and Lynx3 is a potential modulator of this system.