SGK1 (serum/glucocorticoid regulated kinase 1) is a serine/threonine kinase that plays critical roles in cellular stress response, ion transport regulation, and immune modulation 1. The kinase regulates multiple cellular processes including macrophage function, where dexamethasone upregulates SGK1 via glucocorticoid receptors, subsequently activating store-operated calcium entry (SOCE) and PIEZO1 channels, leading to calcium influx and cytoskeletal remodeling 1. In cardiac pathophysiology, SGK1 promotes fibrosis through the PI3Kγ/SGK1 pathway-dependent M2 macrophage polarization 2 and drives pathological cardiac hypertrophy through a novel noncanonical ERAD mechanism called ERAD-Out, where SGK1 itself becomes a degradation target 3. SGK1 demonstrates tumor suppressor activity in hepatocellular carcinoma metastasis by facilitating CD8+ T cell-mediated RIPK1-dependent necroptosis; loss of SGK1 enables immune evasion and metastatic colonization 4. In vascular pathology, SGK1 promotes smooth muscle cell phenotypic transformation in thoracic aortic dissection by phosphorylating SIRT6 at Ser338, leading to SIRT6 degradation and subsequent MMP9 upregulation 5. Additionally, SGK1 exacerbates inflammatory conditions including pulmonary fibrosis through H3K27ac-mediated macrophage reprogramming 6 and rheumatoid arthritis by promoting macrophage pyroptosis via Slc6a12 channels 7. SGK1 dysregulation is implicated in various cancers, making it a potential therapeutic target 8.