ALK (Anaplastic Lymphoma Kinase) is a receptor tyrosine kinase belonging to the insulin receptor superfamily and the ALK/LTK subfamily. Under physiological conditions, ALK is activated by its ligands ALKAL1 and ALKAL2, triggering autophosphorylation at key tyrosine residues (Y1278, Y1282, Y1283) within the activation loop and subsequent downstream signaling. Key substrates include IRS-1, SHC, and STAT3, driving activation of RAS/MAPK, PI3K/AKT, and JAK/STAT pathways that regulate cell proliferation, survival, and differentiation. In cancer, ALK is aberrantly activated through chromosomal translocations producing fusion oncoproteins — most notably EML4-ALK in non-small cell lung cancer (NSCLC) — as well as point mutations and gene amplification seen in anaplastic large cell lymphoma (ALCL), neuroblastoma, and inflammatory myofibroblastic tumors. These oncogenic alterations make ALK one of the most clinically validated and therapeutically actionable kinase targets in oncology, with multiple generations of ALK inhibitors approved and in active clinical development.