Histidinetriad nucleotide-bindingproteins (HINTs) exhibit hydrolytic activity toward nucleoside phosphoramidates,such as tryptamine adenosine phosphoramidate (TrpA) (Figure a). While the biologically relevant substrates of HINT1 have not beenclearly elucidated, the protein has been implicated in opioid receptorsignaling,−,  regulation of the melanoma-associated transcriptionfactor MITF,, and DNA damage repair. These functions position HINT1 as a potentialpharmacological target for treating conditions such as opioid resistanceor melanoma. This evidence concerns the gene MITF and melanoma.