PODXL (podocalyxin like) is a multifunctional cell surface glycoprotein that regulates cell adhesion, migration, and epithelial polarity through diverse mechanisms. The protein functions as both an anti-adhesive molecule in podocytes, maintaining filtration pathways through charge repulsion, and as a pro-adhesive molecule that enhances integrin-dependent cell migration and contacts 1. PODXL plays critical roles in normal development, including spermatogonial stem cell proliferation and apoptosis regulation, where TCF3 transcriptionally targets PODXL to maintain stem cell activity 1. The protein is also involved in pluripotent stem cell biology, serving as a specific marker for pluripotent stem cell-derived extracellular vesicles with >50% positive rates 2. In cancer progression, PODXL exhibits oncogenic properties through multiple mechanisms. It promotes metastatic seeding of circulating tumor cell clusters in breast cancer, particularly when hyposialylated, enabling chemotherapy evasion and cellular quiescence 3. Meta-analysis of 5,705 patients across 10 cancer types demonstrated that high PODXL expression significantly correlates with poor overall survival, particularly in pancreatic cancer, glioblastoma multiforme, and other malignancies 4. Additionally, PODXL expression is altered in neurodevelopmental disorders, with reduced levels observed in schizophrenia patient-derived cerebral organoids 5.