GAREM2 is a brain-specific adapter protein that mediates EGF receptor signaling to the MAPK/ERK pathway 1. Like its ubiquitously expressed homolog GAREM1, GAREM2 contains tyrosine residues (Tyr-102, Tyr-429, Tyr-551) that undergo phosphorylation upon growth factor stimulation, enabling Grb2 binding and subsequent ERK activation 1. However, GAREM2 possesses a unique glycine-rich domain that promotes stimulus-dependent granule formation in the cytoplasm, distinguishing it from the nuclear-localized GAREM1 2. In neuroblastoma cells, GAREM2 regulates both EGF and insulin-like growth factor 1-induced ERK activation and neuronal differentiation 1. GAREM2 knockout mice exhibit reduced anxiety-like behavior and impaired neurite extension in primary neurons, suggesting roles in emotional behavior and neuronal development 3. GAREM2 interacts with Intersectin, a multi-domain adapter regulating endocytosis and signaling 3. Clinically, GAREM2 has relevance to neurodevelopment, with altered DNA methylation of GAREM2 detected in infants exposed to maternal SARS-CoV-2 4. Additionally, GAREM2 mediates MAPK pathway activation in multiple myeloma, promoting cancer cell proliferation 5. These findings establish GAREM2 as a specialized brain-enriched regulator of growth factor signaling with implications for neurodevelopmental and neoplastic diseases.