The present invention describes a newly discovered polynucleotide encoding a protein involved in the cell signaling cascade, called RET16, cloned, isolated and identified from TNF-alpha stimulated human microvascular endothelial cells, as well as mouse and rat RET16 orthologs thereof. Also described are the RET16 polypeptide sequence, expression vectors, host cells, agonists, antagonists, antisense molecules, and antibodies related to the polynucleotide and/or polypeptide of the present invention. Methods for screening for modulators, particularly inhibitors, of the human RET16 protein, and use of the RET16 polynucleotide and polypeptide for therapeutics and diagnostics are described.