Recently, we cloned rgl-1, a putative rat homologue of the Drosophila tumor suppressor oncogene lethal (2) giant larvae (l(2)gl), from the rat brain. Sequence analysis revealed that rgl-1 encodes a 1,036 amino acid polypeptide containing a domain characteristic of WD-40 repeat sequence. It has been suggested that m-tomosyn is expressed in the rat brain, encodes a 1,116 amino acid polypeptide, contains WD-40 repeat sequence, and is homologous to the Drosophila l(2)gl and mouse mgl-1 genes. The comparison of amino acid sequence for m-tomosyn with l(2)gl and mgl-1 proteins using the clustal method showed only 17.8% and 20% amino acid identity, respectively. However, amino acid identity of rgl-1 protein to l(2)gl and mgl-1 proteins is much higher (30.6% and 96.8%, respectively). Therefore, we investigated their biological function in the absence of Saccharomyces cerevisiae SOP1 and SOP2, the yeast homologues of the Drosophila l(2)gl. Functional analysis showed that the expression of the rgl-1 cDNA, but not m-tomosyn, restored partially salt sensitivity in yeast, indicating that rgl-1 is a homologue of lgl family members.