The microphthalmia transcription factor/transcription factor E (MITF-TFE) family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors includes four family members: MITF, TFE3, TFEB and TFEC. The TEF3 protein interacts with transcription regulators such as E2F3, SMAD3, and LEF-1, and is involved in TGF-beta-induced transcription, playing important roles in cell growth, proliferation, and osteoclast and macrophage differentiation. The TFE3 protein also activates hepatic IRS-2 gene, and induces hexokinase II (HK2) and insulin-induced gene 1 (INSIG1); it participates in insulin signaling and could be a therapeutic target for diabetes. Anti-TFE3 staining is the most sensitive and specific indicator of Xp11 translocation renal cell carcinomas. Since alveolar soft part sarcoma (ASPS) is characterized by a specific chromosomal rearrangement resulting in a chimeric transcription factor (ASPSCR1-TFE3).