These droplets are functionally and physically associated with the endoplasmic reticulum (ER), and, therefore, this HIF2α-PLIN2-dependent lipid droplet formation not only favors the accumulation of excess fatty acids possibly as a consequence of reduced fatty acid oxidation but also avoids cytotoxic ER stress which facilitates the progression of ccRCC (Figure 2). This evidence concerns the gene EPAS1 and nonpapillary renal cell carcinoma.