PHACTR1 (phosphatase and actin regulator 1) is a multifunctional actin-binding protein with critical roles in cardiovascular and pulmonary homeostasis. The protein binds G-actin monomers and regulates actin cytoskeleton dynamics, stress fiber formation, and cell motility 12. PHACTR1 exists as multiple splice variants with tissue-specific expression patterns, including brain-specific long transcripts and intermediate transcripts enriched in vascular tissues 3. In endothelial cells, PHACTR1 functions as a PPARγ transcriptional corepressor that promotes endothelial activation and atherosclerosis under disturbed flow conditions 4. The protein translocates from the nucleus under laminar flow to the cytoplasm, modulating its transcriptional activity. Conversely, HEG1 facilitates CUL3-mediated degradation of PHACTR1, promoting eNOS transcription and vasodilation 5. In pulmonary fibrosis, PHACTR1 knockdown inhibits α-SMA and collagen expression in TGF-β-induced fibroblasts, with PHACTR1 knockout reducing inflammation and fibrosis in bleomycin-induced models 6. Genetically, PHACTR1 SNPs, particularly rs9349379, are associated with coronary artery disease, pulse pressure, and myocardial infarction risk in multiple populations 789. These associations suggest PHACTR1 as a key therapeutic target for cardiovascular and pulmonary diseases.