MITF, TFE3 and TFEB are part of the basic helix-loop-helix-leucine zipper family of transcription factors. Each protein encoded by the family of transcription factors can bind DNA. MITF is necessary for melanocyte and eye development and new research suggests that TFE3 is also required for osteoclast development, a function redundant of MITF. The combined loss of both genes results in severe osteopetrosis, pointing to an interaction between MITF and other members of its transcription factor family. In turn, TFEB has been termed as the master regulator of lysosome biogenesis and autophagy. Interestingly, MITF, TFEB and TFE3 separate roles in modulating starvation-induced autophagy have been described in melanoma. Moreover, MITF and TFEB proteins, directly regulate each other’s mRNA and protein expression while their subcellular localization and transcriptional activity are subject to similar modulation, such as the mTOR signaling pathway.