This study characterized the murine osteoclastic protein-tyrosine phosphatase (PTP-oc) promoter located within intron 12 of the Glepp1 gene. A 2-kb DNA fragment containing the putative intronic promoter showed strong promoter activity in pre-osteoclastic RAW264.7 and U937 cells, but not in non-osteoclastic cells. Deletion analyses identified a proximal region with elements required for basal activity, and upstream repressor and enhancer elements. The cell-type-specificity of the promoter was conferred by upstream domains. At least nine conserved response elements, with potential transcription factor binding sites, were identified in both human and murine promoters. EMSA and ChIP indicate the presence of occupied binding sites for Pit-1a, Ikaros-1/2, and D1DR transcription factors in the murine promoter. Site-directed mutagenesis of response elements resulted in down- or up-regulation of promoter activity: some of the effects were different between the murine and human promoter, suggesting that there may be inter-species differences in the regulation of the PTP-oc promoter.