PKZ is a novel and unique eIF2 alpha protein kinase identified in fish. Although PKZ is most homologous to PKR, particularly in the C-terminal catalytic domain, it contains two N-terminal Z-DNA-binding domains (Z alpha 1 and Z alpha 2) instead of the dsRNA binding domains (dsRBDs) in PKR. As a novel member of eIF2 alpha kinase family, the available data suggest that PKZ has some distinct mechanisms for recognition, binding, and B-Z DNA transition. Functionally, PKZ seems to be activated by the binding of Z alpha to Z-DNA and participates in innate immune responses. In this review, we summarize the recent progress on fish PKZ.