Scp160p is an RNA-binding protein containing 14 tandemly repeated heterogenous nuclear ribonucleoprotein K-homology domains, which are implicated in RNA binding. Scp160p interacts with free and membrane-bound polysomes that are dependent upon the presence of mRNA. Despite its presence on cytosolic polysomes, Scp160p is predominantly localized to the endoplasmic reticulum (ER). Accumulation of Scp160p-ribosome complexes at the ER requires the function of microtubules but is independent of the actin cytoskeleton. We propose that the multi-K-homology-domain protein Scp160p functions as an RNA binding platform, interacting with polysomes that are transported to the ER.