CNN3 (calponin 3) is an actin-binding protein that regulates actin cytoskeleton organization and contractility across multiple cell types. As an actin filament-associated protein, CNN3 inhibits actin-activated myosin ATPase activity and stabilizes the actin cytoskeleton 1. In smooth muscle and non-muscle cells, CNN3 participates in cytoskeleton-based activities, with cell type-specific functions regulated by phosphorylation at Ser293/296 in its C-terminal region 2. Structurally, CNN3 localizes dynamically to contractile stress fibers and is critical for coordinating their contractility; CNN3 depletion results in increased, uncoordinated stress fiber contraction and bundle breakage 3. During trophoblast fusion, CNN3 acts as a negative regulator—its phosphorylation-dependent dissociation from F-actin promotes actin cytoskeletal rearrangement required for cell fusion 2. Clinically, CNN3 expression is significantly elevated in glioblastoma and lower-grade gliomas compared to normal brain tissue, correlating with higher WHO grade and poor prognosis 4. CNN3 knockdown inhibited glioma cell proliferation, migration, and invasion through NF-κB pathway suppression 4. Similarly, elevated CNN3 promotes cervical cancer cell proliferation and metastasis via the RPLP1 pathway 5. Bioinformatics studies indicate CNN3 correlates with immune checkpoint molecules and inflammatory pathways, positioning it as a potential immunotherapy target 67.