ABL1 (ABL proto-oncogene 1) is a non-receptor tyrosine kinase belonging to the Abl family, which includes ABL1 and ABL2 (ARG). Under normal physiological conditions, ABL1 activity is tightly regulated through intramolecular autoinhibition, with the SH3 and SH2 domains clamping the kinase domain in an inactive conformation. Activation occurs via displacement of this autoinhibitory clamp by upstream signals, scaffolding proteins, or oncogenic rearrangements. Key substrates include CRKL, STAT5, FAK, and the adaptor protein DOK1, linking ABL1 to cell proliferation, survival, cytoskeletal remodeling, and DNA damage response. In chronic myelogenous leukemia (CML) and a subset of acute lymphoblastic leukemias (ALL), the chromosomal translocation t(9;22) generates the BCR-ABL1 fusion oncoprotein, constitutively activating kinase activity and driving uncontrolled myeloid expansion. This makes ABL1 one of the most validated oncology drug targets in history, and the success of imatinib as a molecularly targeted therapy established the proof-of-concept for kinase inhibitor drug discovery across oncology.