SFRP

sFRP, or secreted frizzled-related protein, refers to a family of soluble glycoproteins that modulate Wnt signaling. In humans, the family includes SFRP1 through SFRP5, with FRZB commonly used as an alternative name for SFRP3. These proteins are secreted and typically contain an N-terminal Frizzled-like cysteine-rich domain that can bind Wnt ligands, followed by a C-terminal domain related to the Netrin family. The overall structure enables interactions with Wnt ligands and, in some cases, with other components of the signaling pathway.

The primary function of sFRPs is to regulate Wnt signaling, usually by sequestering Wnt ligands and preventing their binding to Frizzled receptors, thereby acting as antagonists of canonical and non-canonical Wnt pathways. However, their effects are context-dependent and can be complex; in certain cellular environments or concentrations, sFRPs may enhance or modulate Wnt signaling rather than simply inhibiting it, potentially by altering ligand distribution or receptor availability.

sFRPs participate in developmental processes that rely on Wnt signaling, including patterning and differentiation in tissues such as the nervous system, limbs, and other organs. In adults, they contribute to tissue homeostasis and regeneration. Dysregulation of sFRP activity has been linked to disease, notably cancer, where promoter methylation or other mechanisms can downregulate SFRP expression, contributing to unchecked Wnt signaling. Conversely, altered sFRP expression has also been observed in degenerative conditions and fibrotic diseases, reflecting their broad influence on cell signaling and tissue dynamics.