FRMPD2 is a multi-domain scaffold protein that functions in synaptic signaling and epithelial cell organization. Structurally, it contains an N-terminal KIND domain, a FERM domain that binds phosphatidylinositol 3,4-bisphosphate, and three PDZ domains 1. At synapses, FRMPD2's second PDZ domain specifically binds the C-terminus of NMDA receptor subunits GluN2A and GluN2B, with stronger affinity for GluN2A, implicating it in NMDA receptor-mediated synaptic signaling and potential neurotoxicity 2. In epithelial cells, FRMPD2 localizes to basolateral membranes in an E-cadherin-dependent manner and is essential for tight junction formation 1. FRMPD2 also regulates immune responses by spatially organizing NOD2 signaling complexes at the basolateral compartment of intestinal epithelial cells; notably, Crohn disease-associated truncations of NOD2 impair FRMPD2 interaction 3. Recent evidence suggests FRMPD2 contributes to human brain evolution, with the FRMPD2B paralog implicated in altered synapse signaling in humanized zebrafish models 4. Additionally, FRMPD2 is a key developmental marker for cone photoreceptor cell differentiation 5. These diverse functions underscore FRMPD2's role as a critical spatial organizer of protein complexes in neuronal and epithelial contexts.