Abelson helper integration site-1 (Ahi-1) is a novel oncogene identified based on its common activation in v-abl and myc-induced murine lymphomas. The murine Ahi-1 gene encodes a unique protein with multiple SH3 binding sites, an SH3 domain and multiple WD40-repeat domains. The conserved human homolog (AHI-1) contains an additional coiled-coil domain in its N-terminal region. Both murine and human Ahi-1/AHI-1 genes encode at least three isoforms and thus this gene is also subject to alternative splicing in normal cells. Expression of Ahi-1/AHI-1 is regulated at multiple stages of hematopoiesis in a highly conserved fashion in mouse and humans. It is highly elevated in certain human lymphoma and leukemia cells, including those from patients with cutaneous T-cell lymphomas (CTCL), BCR-ABL chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). AHI-1 is also to be strongly expressed in embryonic hindbrain and forebrain, and AHI-1 may be required for both cerebellar and cortical development in humans. Defects in AHI-1 are the cause of Joubert syndrome, an autosomal recessive brain congenital malformation.