SPRY1 (sprouty RTK signaling antagonist 1) functions as a negative regulator of multiple receptor tyrosine kinase signaling pathways, particularly those involving FGF, EGF, and TGF-β receptors. The protein acts by inhibiting ERK1/2 phosphorylation and downstream Ras signaling cascades, thereby controlling cellular processes including proliferation, differentiation, and epithelial-to-mesenchymal transition 12. SPRY1's regulatory mechanism involves its degradation through ubiquitination; for example, CCL1 binding to AMFR triggers SPRY1 ubiquitination, leading to ERK pathway activation and fibroblast-to-myofibroblast differentiation in pulmonary fibrosis 2. The gene shows significant disease relevance across multiple conditions. SPRY1 deficiency in epidermal keratinocytes drives psoriatic arthritis development through enhanced JAK/STAT signaling and CXCL10 secretion, which activates periarticular macrophages 3. Additionally, SPRY1 downregulation contributes to lipid metabolism dysregulation in psoriasis 4. In pulmonary arterial hypertension, endothelial SPRY1 deficiency associates with pathological angiogenic-metabolic reprogramming 5. Clinically, SPRY1 expression serves as a biomarker in various contexts, including its role in defining dormant myogenic progenitor states 6 and as a predictor of immunotherapy response in esophageal cancer when expressed in exhausted CD8+ T cells 7.