Insight into the regulation of the actions of the protein-tyrosine kinases will be greatly facilitated by the full characterization of the family of protein-tyrosine phosphatases. A search for novel phosphatases resulted in the isolation of a cDNA, termed HLPR, encoding a member of the family of human receptor-like protein-tyrosine phosphatases: its cDNA sequence predicts a protein of 793 amino acids (unglycosylated Mr 87,500) and includes a 121 residue extracellular domain, a single transmembrane segment, and and two tandem intra-cytoplasmic catalytic domains. The HLPR genes is located on human chromosome 20, and the protein it encodes likely plays a fundamental role in the physiology of all cells as its expression appears to be ubiquitous.