The eph family is the largest subfamily of receptor tyrosine kinases (RTKs). Members of this subfamily display specific expression in the developing and adult brain. Recently, cDNAs encoding membrane bound ligands for these receptors have been identified which we have termed LERKs (ligand for eph-related kinases). We report here the isolation of LERK-7 from a human fetal brain cDNA library. LERK-7 encodes a protein of 228 amino acids and is anchored to the membrane by glycosyl-phosphatidylinositol (GPI) linkage. When transfected into CV1/EBNA cells, LERK-7 binds soluble forms of both hek and elk. In addition, a soluble form of LERK-7 will induce phosphorylation of eck expressed in a human duodenum adenocarcinoma cell line. LERK-7 expressed multiple transcripts (7.5-kb, 6.0-kb, and 3.5-kb) with the highest levels in human adult brain, heart, spleen, and ovary and human fetal brain, lung, and kidney. Similar to the other ligands in this family, LERK-7 is developmentally regulated in the brain. LERK-7 is identical to the recently described AL-1.