TFE3 and neoplasm: This study investigates whether <i>TFE3</i> fusion proteins promote <i>TFE3</i> rRCC progression by regulating fatty acid oxidation (FAO).<h4>Methods</h4>To elucidate the regulatory mechanisms, transcriptome sequencing, Western blotting, real-time quantitative PCR, dual-luciferase reporter assays, Chromatin Immunoprecipitation assays, and Seahorse XF96 analysis were employed to examine how TFE3 fusion proteins regulate the PGC-1α/PPARα/CPT1A axis and its impact on mitochondrial FAO in tumor cells.