SPRED2 (sprouty related EVH1 domain containing 2) functions as a negative regulator of the Ras/MAPK signaling pathway, primarily by inhibiting ERK1/2 activation 12. The protein recruits and translocates NF1 to the cell membrane, enabling NF1-dependent hydrolysis of active GTP-bound Ras to inactive GDP-bound Ras, thereby suppressing downstream MAPK signaling cascades. In hepatocellular carcinoma (HCC), SPRED2 acts as a tumor suppressor by inhibiting cell proliferation, migration, and invasion while promoting apoptosis through caspase-3 activation and Mcl-1 downregulation 1. SPRED2 also suppresses cancer cell stemness through a novel p53/miR-506-3p/KLF4 pathway, forming protein complexes with p53 to upregulate miR-506 transcription and subsequently downregulate KLF4 expression 3. Additionally, SPRED2 promotes autophagy by reducing mTORC1 signaling and facilitating mitophagy in both HCC cells and normal hepatocytes 4. In eye development, conditional loss of SPRED2 (along with SPRED1) leads to hyperproliferation of lens epithelial cells and accelerated fiber differentiation due to elevated ERK1/2 signaling 5. SPRED2 mutations are associated with Noonan syndrome 14, and the gene shows evidence of positive selection in clonal hematopoiesis 6. Clinically, reduced SPRED2 expression in HCC correlates with poor prognosis and more malignant phenotypes 2.