Divergent functions of the evolutionarily conserved, yet seemingly dispensable, Wnt target, sp5.

The activation of sp5 in response to Wnt/β-catenin signaling is observed in many species during axis patterning, neural crest induction, maintenance and differentiation of stem cells. Indeed, the conserved response of sp5 orthologs to Wnt-mediated activation is the basis for this gene commonly being used as a readout for Wnt signaling activity. However, several seemingly conflicting findings regarding the function of sp5 in the context of Wnt signaling cast this gene in an enigmatic light. In this review, we examine current knowledge of sp5 structure and function, its relationship to Wnt signaling in varied contexts, and present perspectives on how progress on this interesting gene can move forward.