In the present study, we found that overexpressed TRAF3IP2 in NONO-TFE3 tRCC could enhance tumor progression through function as a co-activator of NOTCH1 to mediate NOTCH1 target genes. This evidence concerns the gene TRAF3IP2 and renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.