ANKFY1 (ankyrin repeat and FYVE domain containing 1) is a Rab5 effector protein that functions as a critical regulator of endosomal trafficking and cell migration. Primary Function: ANKFY1 binds phosphatidylinositol 3-phosphate (PI3P) and acts as a Rab5-GTP effector to coordinate homotypic early endosome fusion and macropinocytosis 1. The protein localizes to endosomal membranes and regulates retromer complex subcellular localization in an EHD1-dependent manner, controlling endosome-to-Golgi transport and biosynthetic transport to late endosomes and lysosomes 2. Mechanism: ANKFY1 mediates internalization and trafficking of activated receptor tyrosine kinases such as PDGFRB 3 and is required for proper cell surface VEGFR2 levels in retinal endothelial cells through the Akt/eNOS pathway 4. The protein interacts physically with MYO5A to facilitate intracellular transport 5. Disease Relevance: ANKFY1 mutations cause steroid-resistant nephrotic syndrome (SRNS) through impaired RAB5 binding and reduced podocyte migration capacity 6. The gene is also implicated in Alzheimer's disease, showing differential DNA methylation in patient blood samples 7. Clinical Significance: ANKFY1 promotes osteogenic differentiation of bone marrow mesenchymal stem cells and may represent a therapeutic target for osteoporosis management 8.