Gelsolin (GSN) is a calcium-regulated actin-binding protein that functions as a multifaceted cytoskeletal regulator with emerging roles in inflammatory and cardiovascular disease. Primary functions include actin filament capping, severing, and nucleation activities that organize the cytoskeleton 1. GSN also participates in ciliogenesis 2. Mechanistically, GSN regulates actin dynamics through calcium-dependent binding to actin filament barbed ends. Beyond cytoskeletal roles, GSN negatively regulates NLRP3 inflammasome activation in macrophages by interacting with NLRP3 and preventing its mitochondrial translocation, thereby maintaining intracellular calcium equilibrium and mitochondrial stability 3. In cardiac pathophysiology, GSN is a direct target of NAE1 (NEDD8-activating enzyme), where increased NAE1 crotonylation promotes GSN neddylation and protein stability, enhancing GSN's actin-severing activity and driving pathological cardiac hypertrophy and cytoskeletal remodeling 4. Disease relevance includes hereditary systemic amyloidosis (Finnish type), associated with GSN mutations 5. Notably, plasma GSN levels are significantly reduced in rheumatoid arthritis patients, and GSN-deficient mice exhibit exacerbated arthritic symptoms and enhanced inflammatory responses across multiple disease models including sepsis and acute kidney injury 3. These findings establish GSN as both a diagnostic biomarker and therapeutic target for inflammatory and cardiovascular diseases.