PHACTR3 (phosphatase and actin regulator 3), also known as scapinin, is a multifunctional protein primarily involved in actin cytoskeleton regulation and cell morphogenesis. The protein contains a putative regulatory subunit domain for protein phosphatase-1 (PP1) and binds directly to cytoplasmic actin 1. PHACTR3 localizes to the plasma membrane through basic and hydrophobic residues in its N-terminus, where it concentrates in lamellipodia and membrane ruffles to regulate actin dynamics and morphological changes in cells 2. The protein is predominantly expressed in mammalian brain tissue with complex, tissue-specific transcription patterns during development 1, suggesting specialized neurological functions. Clinically, PHACTR3 has emerged as a significant biomarker in cancer diagnostics. DNA methylation of PHACTR3 is progressively increased during HPV-induced cervical carcinogenesis, appearing in up to 100% of cervical carcinomas 3, and serves as a triage marker for detecting high-grade cervical disease 4. In colorectal cancer, PHACTR3 methylation shows 70-fold increased levels in advanced neoplasia, demonstrating 66% sensitivity and 100% specificity for CRC detection in stool samples with complementary value to fecal immunochemical testing 5. PHACTR3 methylation also appears useful for bladder cancer detection in urine 6 and lung cancer diagnosis 7, and shows prognostic significance in left-sided colon cancer 8.