Allelic loss at chromosome 3p21.3 is the most frequent and the earliest genetic alteration in lung cancer, implying the presence of one or more critical tumor suppressor genes (TSGs) in this region.1– Identifying these genes and translating the knowledge into clinical practice should facilitate the development of novel therapeutics, and new early detection and prevention strategies for lung cancer. H37, also known as Luca15/RBM5, is one of the approximately 35 genes located in this 370-kilobase tumor suppressor locus.2 We have demonstrated that H37 has the characteristics of a TSG. There is reduced expression of the H37 gene and/or reduced protein expression in 80% of primary non-small cell lung cancers, and the transfection of H37 shows growth-inhibitory properties both in vivo and in vitro.3 Currently, we are trying to confirm H37 as a bona fide TSG and to evaluate the potential of H37 as a therapeutic or molecular marker in lung cancer by implementing the following three strategies. First, we are examining the methylation status of the H37 gene promoter in lung cancer patient samples to determine whether H37 has utility as a tumor diagnostic/prognostic marker. Second, we are generating conditional knockout mice to study the roles of H37 in normal lung development and lung cancer formation in an animal model. Last, we are investigating the molecular mechanism of H37 growth regulation and the interactions of H37 with other important molecules in lung cancer, with a long-term goal of developing rationally designed, targeted therapies. Ultimately, our present studies may serve as a foundation for developing new diagnostic and therapeutic regimens for human lung cancers containing alterations in the H37 gene.