The present invention relates to regulation of cellular proliferation. More particularly, the present invention is directed to nucleic acids encoding LETM1 ("leucine zipper EF hand transmembrane receptor"), which is involved in modulation of cellular proliferation and cell cycle regulation. The invention further relates to methods for identifying and using agents, including small molecule chemical compositions, antibodies, siRNA, antisense nucleic acids, and ribozymes, that modulate cell cycle regulation and cellular proliferation via modulation of LETM1 and LETM1 related signal transduction; as well as to the use of expression profiles and compositions in diagnosis and therapy related to cell cycle regulation and modulation of cellular proliferation.