The vertebrate syndecans, which make up a four-member family of small type I transmembrane heparan sulfate proteoglycans, constitute evolutionarily conserved family proteins. In particular, sequences in the transmembrane and cytoplasmic domains are a unifying feature within the family. However, the extracellular domain sequences are molecule-specific, implying that different syndecans have evolved to carry out similar, but non-identical, functions. While all four syndecans have been implicated in regulation of the cytoskeleton, their roles are clearly complex. Recent developments indicate that the closely related syndecan-2 and -4 have separable functions, though both bind a number of ligands through their heparan sulfate chains. The specification of these activities is probably core protein related, but is it due to a distinct expression pattern or molecule-specific regulatory mechanisms? Although there is not yet enough data to provide unambiguous answers, here we shall review the known functions and regulatory mechanisms of syndecan-2 and -4.