MSRAs (methionine sulfoxide reductases A) are enzymes that reverse the effects of oxidative damage by reducing methionine sulfoxide back to methionine and recovering protein function. In this study we demonstrate that the transcriptional regulation of the human MSRA gene is complex and driven by two distinct promoters. Both promoters demonstrate high expression in human brain and kidney tissues. The upstream (promoter 1) regulates the msrA1 transcript that codes for the mitochondrial form of MSRA and is highly active in a broad range of cell lines. The downstream promoter (promoter 2) regulates the msrA2/3 transcripts that code for the cytosolic/nuclear forms of MSRA and is generally less active. Promoter 2 contains a 65 bp putative enhancer region that is very active in the retinal pigment epithelium-derived D407 cell line. Both promoters are partially regulated by all-trans retinoic acid via RARA and other RARs.