The transmembrane E3 ubiquitin ligases ZNRF3 and RNF43 are negative regulators of β-catenin and the Wnt signaling pathway in eukaryotic cells. The activity of ZNRF3 can be modulated by antibody binding to its extracellular domain, thus causing an increase in Wnt signaling. The ZNRF3 antagonizing antibodies can be used to treat diseases with low Wnt signaling, such as short bowel syndrome, osteoporosis, diabetes, neurodegenerative diseases, and mucositis. In addition, the antagonizing antibodies of the invention can be used to enhance Wnt signaling for tissue repair and wound healing.
