Some zinc finger proteins can recognize and bind to specific target RNA molecules, and participate in or mediate important biological functions in cells. This discovery expanded people's understanding of dedicated transcriptional regulation of zinc finger proteins which highly depends on specific binding to target DNA sequences. ZNF638/NP220 and its homologous proteins Matrin3 and RBM20 form a class of special zinc finger proteins that are quite conservative in biological evolution. They are located in the nuclear plaques of the nuclear matrix, containing both zinc finger motifs that recognize DNA and conserved RNA-binding domains specifically targeting RNA molecules. Such properties imply special roles in the different stages of cell transcriptional regulation and RNA processing, especially in the coupling of RNA transcription and splicing events, as well as in changing the maturity and stability of RNA molecules. This article summarized the advances in recent studies with regards to genetic discoveries, structural analyses, molecular mechanisms and biological functions of ZNF638 and its homologs, and their potential influences on cell differentiation, embryonic development, virus infection and other life processes.