Cellular signaling and biological functions of R-spondins

R-spondins (RSPOs) are a family of cysteine-rich secreted proteins containing a single thrombospondin type I repeat (TSR) domain. A vast amount of information regarding cellular signaling and biological functions of RSPOs has emerged over the last several years, especially with respect to their roles in the activation of the WNT signaling pathway. The identification of several classes of RSPO receptors may indicate that this family of proteins can affect several signaling cascades. Herein, we summarize the current understanding of RSPO signaling and its biological functions, and discuss its potential therapeutic implications to human diseases.

► R-spondins are cysteine-rich, thrombospondin type I repeat containing proteins.
► R-spondins activate WNT signaling pathways through multiple receptors.
► R-spondin gene mutations are associated with human genetic diseases.
► R-spondins are essential for various developmental processes in mice and frogs.