We report a novel putative serine/threonine protein kinase containing a leucine-zipper domain, isolated from an human neuronal cell line. The teratocarcinoma cell line NT2 was differentiated to postmitotic NT2-N neurons by treatment with retinoic acid, and degenerate oligonucleotide primers to the catalytic domains of protein kinases were employed to PCR amplify subtractive cDNAs. We identified a clone, represented at higher abundance in NT2-N neurons than in the parental cell line, which encodes a putative serine/threonine kinase of 859 [corrected] amino acids, the leucine-zipper protein kinase (zpk). Zpk protein contains a leucine-zipper domain, found in many DNA-binding proteins, but few protein kinases. Steady-state mRNA levels for zpk are high in human brain and kidney. Further studies are required to evaluate the role of zpk in neuronal differentiation.