Can dephosphorylate single and diphosphorylated synthetic MAPK peptides, with preference for the phosphotyrosine and diphosphorylated forms over phosphothreonine. In vitro, dephosphorylates p-nitrophenyl phosphate (pNPP). In bone tissue, upon activation of the G(q)-dependent KISS1/KISS1R signaling pathway, DUSP18 is recruited to the KISS1R C-terminus where it dephosphorylates SRC, resulting in down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity). {ECO:0000250|UniProtKB:Q8VE01, ECO:0000269|PubMed:12408986, ECO:0000269|PubMed:12591617}. This is the function of DUSP18 (dual specificity phosphatase 18, ENSG00000167065).