TFE3, also known as transcription factor binding to IGHM enhancer 3, is a member of the MiT family of the bHLH-leucine zipper transcription factor. It plays a crucial role in various biological processes such as autophagy, lysosomal activity, and metabolic regulation [2,5]. It participates in energy metabolism by regulating glucose and lipid metabolism, mitochondrial metabolism, and autophagy pathways [5]. TFE3 also has a significant impact on processes like insulin gene expression and glucose homeostasis [6].

In renal cell carcinoma, TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare subtype. It is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion and certain somatic copy number alterations are related to aggressive features and poor outcomes [1]. TFE3-immunopositive papillary renal cell carcinoma without TFE3 gene rearrangement shows a poorer prognosis and is associated with autophagy/lysosome protein expressions [3]. In TFE3-rearranged perivascular epithelioid cell tumors (PEComas), about 11% cases are diagnosed post-chemotherapy, and most have a poor prognosis [4]. Also, in Birt-Hogg-Dubé (BHD) syndrome, TFE3, along with TFEB, drives kidney cystogenesis and tumorigenesis [7].

In conclusion, TFE3 is a key regulator in multiple biological processes. Its role in autophagy, metabolic regulation, and especially in various kidney-related diseases and tumors has been well-demonstrated through studies. The research on TFE3-related models has provided valuable insights into understanding the mechanisms of these diseases and may guide the development of new therapeutic strategies.