CNN2 (calponin 2) is an actin-binding protein that stabilizes the actin cytoskeleton and regulates smooth muscle and non-muscle cell functions 1. The protein inhibits actin-activated myosin ATPase activity and is expressed in both smooth muscle and diverse non-muscle tissues, where it executes cell type-specific physiological roles 1. Mechanistically, CNN2 interacts with regulatory proteins including calmodulin and tropomyosin to modulate actin filament organization and cytoskeleton tension 1. Beyond structural functions, CNN2 regulates ketogenesis in kidney injury by interacting with estrogen receptor 2 (ESR2) to control mitochondrial sirtuin 5 activity 2. CNN2 is also targeted for proteasomal degradation by the CRL3GIG ubiquitin ligase complex, which maintains neurofilament homeostasis 3. Clinically, CNN2 dysregulation associates with multiple pathologies: it promotes colorectal cancer development through EGR1-dependent mechanisms 4, regulates amyloid-β and tau proteostasis in Alzheimer's disease models 5, influences osteogenic differentiation through miR-873-3p-mediated pathways relevant to osteoporosis 6, and serves as a biomarker for ectopic pregnancy 7. These diverse functions reflect CNN2's pivotal role in regulating cytoskeletal dynamics across multiple physiological and pathological contexts.