TAGLN3 (transgelin 3) is an actin-binding protein that belongs to the calponin family and plays crucial roles in cytoskeletal regulation and cellular signaling 1. The protein functions primarily through actin filament binding and organization, contributing to actin-myosin interactions and maintaining actin filament stability 1. TAGLN3 serves as a critical regulator of neuroinflammation, particularly in astrocytes where it modulates NF-κB activation. APOE4, a major Alzheimer's disease risk factor, specifically downregulates TAGLN3 expression through histone deacetylase activity, leading to chr3 inflammation and hyperactivated inflammatory responses 2. In pancreatic β-cells, TAGLN3 knockout affects sensitivity to lipotoxicity, suggesting involvement in diabetes pathogenesis 3. The gene demonstrates significant disease relevance across multiple conditions. TAGLN3 is downregulated in sporadic Alzheimer's disease patient brains and identified as a shared genetic signature between Alzheimer's disease and diabetes-associated cognitive dysfunction 24. Proteomic studies reveal altered TAGLN3 levels in cerebrospinal fluid of mild cognitive impairment patients 5. Additionally, differential methylation patterns of TAGLN3 are associated with preterm birth effects persisting into adulthood 6. These findings position TAGLN3 as a potential therapeutic target and biomarker for neuroinflammation and neurodegenerative diseases.