MITF is a master transcription factor regulating melanocyte development, survival, and differentiation by binding M-boxes and E-boxes in promoters of pigmentation genes including tyrosinase and TYRP1 12. MITF functions as a lineage-survival oncogene in melanoma, where it coordinates multiple biological processes including proliferation, differentiation, and metabolism 3. The factor exhibits remarkable functional selectivity: acetylation at K206 by p300/CBP reduces DNA-binding residence time and preferentially directs binding from differentiation-associated CATGTG motifs toward CACGTG elements, thereby suppressing differentiation 3. Beyond transcriptional roles, MITF undergoes S325 phosphorylation upon DNA damage, remodeling its protein interactome to interact with the MRN complex and impair homologous recombination repair, thereby increasing genomic instability 4. MITF regulates an antioxidant program protecting melanoma cells from ROS-induced damage through direct binding to E-box sequences near IDH1 and NNT promoters 5. In melanoma plasticity, MITF promotes the melanocytic/proliferative phenotype by suppressing TFE3 through activation of non-canonical mTORC1 pathway components 6. MITF responds to nutrient availability through mTOR-mediated phosphorylation: starvation or lysosomal stress induces dephosphorylation and transcriptional activation 7. Disease-relevant mutations include K206Q (Waardenburg syndrome) and E318K (melanoma predisposition), highlighting the clinical significance of post-translational modifications in MITF function.