The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase was initially 
discovered as a component of the fusion protein nucleophosmin (NPM)-ALK in 
anaplastic large-cell lymphoma (ALCL). Genomic alterations in ALK, including 
rearrangements, point mutations, and genomic amplification, have now been 
identified in several malignancies, including lymphoma, non-small cell lung 
cancer (NSCLC), neuroblastoma, inflammatory myofibroblastic tumor, and others. 
Importantly, ALK serves as a validated therapeutic target in these diseases. 
Several ALK tyrosine kinase inhibitors (TKI), including crizotinib, ceritinib, 
and alectinib, have been developed, and some of them have already been approved 
for clinical use. These ALK inhibitors have all shown remarkable clinical 
outcomes in ALK-rearranged NSCLC. Unfortunately, as is the case for other kinase 
inhibitors in clinical use, sensitive tumors inevitably relapse due to acquired 
resistance. This review focuses on the discovery, function, and therapeutic 
targeting of ALK, with a particular focus on ALK-rearranged NSCLC.