SOCS2 (suppressor of cytokine signaling 2) functions as a substrate-recognition component of cullin-5-RING E3 ubiquitin-protein ligase complexes that mediate targeted protein degradation 1. The protein specifically recognizes phosphorylated substrates through its SH2 domain and promotes their K48-linked polyubiquitination and proteasomal degradation 1. SOCS2 acts as a negative regulator of cytokine signaling by targeting key receptors including growth hormone receptor (GHR) and erythropoietin receptor (EPOR) for degradation following their JAK2-mediated phosphorylation. In hepatocellular carcinoma, SOCS2 promotes radiosensitization by enhancing ubiquitination and degradation of SLC7A11, ultimately leading to ferroptosis 1. The protein also plays important roles in neuroinflammation, where it mediates anti-inflammatory effects downstream of type I interferons in astrocytes during CNS autoimmunity 2. SOCS2 expression is dysregulated in various cancers, with downregulation observed in colorectal cancer where it may serve as a diagnostic biomarker 3. Additionally, SOCS2 is targeted by microRNA-9-5p in depression, contributing to microglial M1 polarization and neuroinflammation 4. The gene shows therapeutic relevance in hepatitis B treatment, where higher expression correlates with improved interferon response 5.