SMTN (smoothelin) is a cytoskeletal structural protein predominantly expressed in contractile smooth muscle cells, with two tissue-specific isoforms: smoothelin-A in visceral tissues and smoothelin-B in vascular tissues 1. The protein contains a C-terminal calponin homology domain characteristic of the smoothelin family 2. SMTN functions as a structural component of the contractile apparatus and influences the contractile potential of smooth muscle cells 2. Mechanistically, SMTN specifically interacts with the mechanosensitive domain 21 of filamin A (FLNA), a key actin cross-linking protein, suggesting a role in mechanotransduction and force-dependent cellular regulation 3. SMTN shows dynamic localization in living cells, with its mobility regulated by Rho-kinase signaling and FLNA binding 3. Disease relevance includes associations with cardiovascular pathology: genetic variants in the SMTN gene show significant haplotype associations with cerebral infarction in men 4 and myocardial infarction in women 5. Additionally, SMTN is downregulated in prostate cancer and may serve as a potential biomarker for prostate cancer progression and aggressiveness 6. These findings position SMTN as both a structural regulator of smooth muscle contractility and a genetic modifier of cardiovascular disease risk.