ABL-family proteins comprise one of the best conserved branches of the tyrosine 
kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 
2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity 
and is common among nonreceptor tyrosine kinases. This cassette is coupled to an 
actin-binding and -bundling domain, which makes ABL proteins capable of 
connecting phosphoregulation with actin-filament reorganization. Two vertebrate 
paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 
includes nuclear localization signals and a DNA binding domain through which it 
mediates DNA damage-repair functions, whereas ABL2 has additional binding 
capacity for actin and for microtubules to enhance its cytoskeletal remodeling 
functions. Several types of posttranslational modifications control ABL 
catalytic activity, subcellular localization, and stability, with consequences 
for both cytoplasmic and nuclear ABL functions. Binding partners provide 
additional regulation of ABL catalytic activity, substrate specificity, and 
downstream signaling. Information on ABL regulatory mechanisms is being mined to 
provide new therapeutic strategies against hematopoietic malignancies caused by 
BCR-ABL1 and related leukemogenic proteins.