We report here the isolation of two genes from the yeast, Saccharomyces cerevisiae, that encode proteins closely related to mammalian p40/laminin receptor precursors (LRPs). The yeast genes, designated YST1 and YST2, encode proteins with over 95% amino acid sequence identity with one another and over 60% identity with the human p40/laminin receptor precursor. The Yst/p40/37-LRP proteins are also more distantly related to the S2 family of ribosomal proteins. Analysis of the distribution of Yst1 tagged with the c-myc epitope revealed that the Yst proteins are components of the 40 S ribosomal subunit. Disruption of either YST1 or YST2 causes a significant reduction in growth rate, while disruption of both genes is lethal. Compared to wild type, polysome profiles in strains lacking either YST1 or YST2 show a pronounced shift from larger to smaller polysomes. This shift is accompanied by a substantial increase in free 60 S subunits and reduced levels of 40 S subunits. We conclude that the Yst proteins are required for translation and contribute to the assembly and/or stability of the 40 S ribosomal subunit.