Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene. MITF is a basic helix-loop-helix leucine zipper transcription factor involved in lineage-specific pathway regulation of many types of cells including melanocytes, osteoclasts, and mast cells. The term "lineage-specific", since it relates to MITF, means genes or traits that are only found in a certain cell type. Therefore, MITF may be involved in the rewiring of signaling cascades that are specifically required for the survival and physiological function of their normal cell precursors. MITF, together with transcription factor EB (TFEB), TFE3 and TFEC, belong to a subfamily of related bHLHZip proteins, termed the MiT-TFE family of transcription factors. The factors are able to form stable DNA-binding homo- and heterodimers. The gene that encodes for MITF resides at the mi locus in mice, and its protumorogenic targets include factors involved in cell death, DNA replication, repair, mitosis, microRNA production, membrane trafficking, mitochondrial metabolism, and much more. Mutation of this gene results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. In human subjects, because it is known that MITF controls the expression of various genes that are essential for normal melanin synthesis in melanocytes, mutations of MITF can lead to diseases such as melanoma, Waardenburg syndrome, and Tietz syndrome. Its function is conserved across vertebrates, including in fishes such as zebrafish and Xiphophorus. An understanding of MITF is necessary to understand how certain lineage-specific cancers and other diseases progress. In addition, current and future research can lead to potential avenues to target this transcription factor mechanism for cancer prevention. Clinical significance Mutations As mentioned above, changes in MITF can result in serious health conditions. For example, mutations of MITF have been implicated in both Waardenburg syndrome and Tietz syndrome. Waardenburg syndrome is a rare genetic disorder. Its symptoms include deafness, minor defects, and abnormalities in pigmentation. Mutations in the MITF gene have been found in certain patients with Waardenburg syndrome, type II. Mutations that change the amino acid sequence of that result in an abnormally small MITF are found. These mutations disrupt dimer formation, and as a result cause insufficient development of melanocytes. The shortage of melanocytes causes some of the characteristic features of Waardenburg syndrome. Tietz syndrome, first described in 1923, is a congenital disorder often characterized by deafness and leucism. Tietz