This project aims to elucidate the role of the RNA-binding protein TIA1 in regulating synaptic RNA metabolism and neuronal plasticity under physiological and chronic stress conditions. Although TIA1 is a key component of stress granules and a critical modulator of RNA processing and translational control, its specific contribution to local synaptic protein synthesis and plasticity remains largely unknown. Given that persistent stress granule formation and RBP dysregulation are linked to stress-related disorders such as depression and Alzheimer’s disease, we will investigate how TIA1 influences synaptic translation, neuronal function, and behavior. Using an interdisciplinary approach that integrates in vivo calcium imaging, molecular and proteomic profiling (including proximity labeling and RNA immunoprecipitation sequencing), and behavioral assessments of cognition and emotional states, we aim to define TIA1-associated synaptic mRNAs and protein interactors and determine how chronic stress alters these networks. This comprehensive strategy will provide novel mechanistic insights into how TIA1-mediated RNA regulation contributes to synaptic dysfunction and cognitive impairment in stress-related neuropsychiatric and neurodegenerative conditions.