The proteoglycanase clade of the ADAMTS superfamily shows preferred proteolytic activity towards the hyalectan/lectican proteoglycans: aggrecan, brevican, neurocan and versican. ADAMTS15, a member of this clade, was recently identified as a putative tumour suppressor gene in colorectal and breast cancer. However, its biosynthesis, substrate specificity and tissue expression are poorly described. Therefore, we undertook a detailed study of this proteinase and expression of the gene. We report the propeptide processing of the ADAMTS15 zymogen by furin activity, identifying RAKR↓212 as a major furin cleavage site within the prodomain. ADAMTS15 is activated extracellularly, present in the pericellular matrix and requires propeptide processing before cleaving V1 versican at position E441↓A442. In the mouse embryo, Adamts15 is expressed in the developing heart at E10.5 and E11.5 dpc, and in the musculoskeletal system from E13.5 through E15.5 dpc. Adamts15 is also highly expressed in several structures within the adult mouse colon. Our findings show overlapping sites of Adamts15 expression with other members of ADAMTS proteoglycanases during embryonic development, suggesting possible cooperative roles during embryogenesis, previously noted in other ADAMTS proteoglycanase combinatorial knockout mouse models. Collectively, these data indicate a possible role for ADAMTS15 in a wide range of biological processes that are potentially mediated through the processing of versican.