FLOT2 is a lipid raft-associated scaffolding protein that participates in membrane organization and cellular polarization. It localizes to caveolar and vesicular compartments where it organizes cytoskeletal architecture and regulates adhesion molecules including CD44. FLOT2 is consistently overexpressed across multiple cancer types—including acute myeloid leukemia, chr17 myeloid leukemia, colorectal carcinoma, breast cancer, cervical cancer, glioma, nasopharyngeal carcinoma, and diffuse large B-cell lymphoma—where elevated expression correlates with aggressive disease features and poor prognosis 123456. In chr17 myeloid leukemia specifically, FLOT2 is required for leukemia-initiating cell homing through a CD44-CDC42 axis 1. FLOT2 also promotes cancer cell invasion and epithelial-mesenchymal transition through activation of the MEK/ERK pathway 57. Beyond cancer, FLOT2 protects podocytes in diabetic nephropathy by stabilizing synaptopodin, and participates in osteoclast differentiation in bone homeostasis 89. Post-translational deacetylation by HDAC6 maintains FLOT2 protein stability in nasopharyngeal carcinoma 3. Recent evidence suggests FLOT2-targeting strategies—including siRNA approaches and small-molecule inhibitors—represent therapeutic opportunities in leukemia and solid tumors, with FLOT2-siRNA showing potential in preclinical models of breast cancer-induced bone loss 9.