In a ccRCC model, Feng et al. discovered that extracellular vesicles derived from M2-polarised macrophages transport miR-342-3p to target and inhibit NEDD4L, thereby blocking the ubiquitination and degradation of CEP55 and activating the PI3K/AKT/mTOR pathway. Here, AKT1 is linked to nonpapillary renal cell carcinoma.