SPRY2 (sprouty RTK signaling antagonist 2) functions as a key regulator of receptor tyrosine kinase (RTK) signaling pathways with context-dependent effects on cellular metabolism and cancer biology. SPRY2 acts as an antagonist of fibroblast growth factor (FGF) signaling by inhibiting FGF-mediated phosphorylation of ERK1/2 and promoting FGFR1 degradation through enhanced c-CBL-mediated ubiquitination 1. The protein also inhibits clathrin- and caveolae-mediated endocytosis of FGFR1 while reducing phospholipase Cγ1 binding to the receptor 1. In contrast, SPRY2 enhances EGFR signaling by inhibiting EGFR endocytosis, ubiquitination, and degradation 1. SPRY2 plays important roles in glucose and lipid metabolism, as knockout studies in hepatocytes demonstrate increased glucose uptake and lipid droplet accumulation 2. The gene shows disease relevance across multiple conditions: SPRY2 loss promotes prostate cancer progression through enhanced ErbB trafficking and PI3K/AKT signaling 3, while decreased SPRY2 expression in cancer-associated fibroblasts correlates with worse breast cancer prognosis and promotes tumor growth 4. Additionally, SPRY2 mutations are associated with congenital hypogonadotropic hypogonadism 5 and vascular dementia 6, highlighting its broad clinical significance in developmental disorders, metabolic diseases, and cancer.