In most mammals, the main and accessory olfactory systems detect of a variety of (semio)chemicals, many of which mediate olfactory-driven social and sexual behaviors. In general, chemosensation depends on G protein-coupled receptors (ORs, TAARs, V1Rs, V2Rs, FPR-rs proteins) that operate at remarkably low stimulus concentrations, thus, indicating highly sensitive and efficient signaling pathways. We therefore hypothesized (i) that signaling cascade proteins are organized in microdomains to ensure optimal signal transduction, and (ii) that the assembly of these domains involves scaffolding proteins. In the SPP 1392 project proposal, we aimed to identify and investigate PDZ domain-containing proteins as putative molecular organizers of signal transduction in chemosensory neurons. Accordingly, a major goal of this research was to analyze the functional role of scaffolding proteins in shaping ultrasensitive and highly selective chemosensory responses. For example, SLC9A3R1, a prototypical scaffolding protein that contains two PDZ domains and a carboxy-terminal ezrin-binding domain, was among the candidate proteins we were interested in. While we initially planned to specifically focus on SLC9A3R1 and its role in the mouse vomeronasal organ, we extended our research during the course of the project to a variety of proteins with similar functions and we also investigated cluster formation of prominent signaling components both in the main and accessory olfactory systems. Together, our tandem project revealed several mechanisms of transduction cascade organization in peripheral chemosensory neurons.