Graphical abstract. Galectin-9 controls cell rear contractility. Left: Galectin-9 binds to glycosylated residues on CD44 inducing CD44 clustering. This facilitates a functional interaction between CD44 and RhoA-GDP, priming RhoA for activation by GEF-H1. RhoA activation leads to actin contractility at the cell rear and migration. In the absence of galectin-9 (right panel), CD44 clustering is deficient, which results in defective RhoA activation and impaired uropod retraction and migration. Created in BioRender. Franken, G. (2025) https://BioRender.com/9zh1jyh.