Anaplastic lymphoma kinase was first described in 1994 as the NPM-ALK fusion protein that is expressed in the majority of anaplastic large-cell lymphomas. About 2/3rds of anaplastic large-cell lymphomas possess a balanced chromosomal translocation in which the entire nucle-ophosmin (NPM) gene on chromosome 5 is fused to the 3' portion of the ALK gene (including the entire intracellular segment with its protein kinase domain) on chromosome 2. This oncogenic ALK protein kinase is a chimeric protein created by a translocation between chromosomes(2;5)(p23;q35) that generates the NPM-ALK fusion protein. NPM-ALK also known as p80, since the chimeric protein weighs 80 kDa. Studies of NPM-ALK have identified pTyr1096 as the binding site for insulin receptor substrate 1 (IRS1); pTyr1507 is the binding site for Shc and pTyr1604 is the binding site for PLC-Y (native human ALK receptor residue numbers are given; subtract 940 to obtain the NPM-ALK residue). (PMID: 23201355, PMID: 33466277)