Syndecans are important mediators of signalling by transmitting external stimuli 
into the cells. This role in signal transduction has been attributed mainly to 
the membrane-bound syndecans. In the last years, however, the soluble ectodomain 
of syndecans generated by shedding has come into the focus of research as this 
process has been show to modulate the syndecan-dependent signalling pathways, as 
well as other pathways. This review summarizes the current knowledge about the 
induction of syndecan shedding and the different pathways modulated by shed 
syndecan proteins. This review summarizes the known and putative sheddases for 
each syndecan and describes the exemplary conditions of sheddase activity for 
some syndecans. This review summarizes the proposed use of shed syndecans as 
biomarkers for various diseases, as the shedding process of syndecans depends 
crucially on tissue- and disease-specific activation of the sheddases. 
Furthermore, the potential use of soluble syndecans as a therapeutic option is 
discussed, on the basis of the current literature. LINKED ARTICLES: This article 
is part of a themed section on Translating the Matrix. To view the other 
articles in this section visit 
http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc.