A protein recently described as a desmosome-specific molecule involved in anchoring intermediate-sized filaments (IFs) to the desmosomal plaque, and hence named "pinin" [43], has been known in our laboratory for several years as a strictly nuclear protein occurring in a wide range of cell types, including many that are totally devoid of desmosomes. Using a series of specific antibodies we have localized the protein in the nucleoplasm of cultured cells, blood cells and solid tissues of diverse vertebrate species, from oocytes to erythrocytes of amphibia and from liver to connective tissue and fibroblasts in mammals. Desmosomes have consistently been negative, and the nuclear specificity of the immunolocalization reactions has also been directly demonstrated by double-label immunofluorescence microscopy. From our results we conclude that this nuclear protein, characterized by a domain exceptionally rich in serine residues and hence termed DRS-protein, occurs in at least two genetically different forms in a diffusible state as well as in special ribonucleoprotein-particles, "speckles" [6], and is a widespread if not ubiquitous nuclear protein. Consequently it must serve nuclear functions rather than "pinning" IFs to plasma membranes and does not provide a new reliable marker for desmosomes and epithelial or myocardial differentiation.