Secreted frizzled-related proteins control a multitude of biological phenomena throughout development and adult life in humans. In parallel, aberrant gene expression and abnormal secreted protein levels accompany a wide range of pathologies in humans. In this review, we provide a brief introduction to sFRP4, an update of the pathways it's involved, its various physiological actions that are reported to contribute to diseases, outlining the importance of its wider research and specific modulation by pharmacologic interventions. First recognized as a novel molecule that co-purified with a disparate protein, its identity was based on its sequence homology to the frizzled receptors. Once multiple members of the family were cloned, their genetic loci, tissue and subcellular distributions were located. Nucleotide and amino acid sequences were characterized and homology to different organisms was found to be present that helped elucidate their actions. Following subsequent experimental studies, they were found to be secreted proteins with an affinity to bind to the Wnt ligands, participating in different developmental and adult homeostatic pathways by the virtue of their regulatory function to the Wnt signal transduction system. Secreted frizzled related protein 4 has garnered considerable attention in the recent years following breakthrough discoveries implicating them in the pathogenesis of various diseases. Studies investigating them can provide information not only regarding their association with a disease but can also help use them as potential biomarkers and therapeutic targets.