PIPKI-PIP2 promotes cell migration by recruiting Smurf1 to the membrane and increasing its activity

• PIP2 and PIPKI regulate the membrane translocation of Smurf1, a key E3 ubiquitin ligase. • The C2 domain of Smurf1 directly binds to PIP2, which is essential for its membrane recruitment and E3 ligase activity. • The PIPKI-PIP2-Smurf1 signaling axis is critical for cell migration, offering a potential therapeutic target in cancer. • This study provides mechanistic insight into how membrane localization controls Smurf1 function, with implications for understanding cell polarity and migration.