ALK (anaplastic lymphoma kinase) is a transmembrane receptor tyrosine kinase, 
initially discovered as part of the NPM-ALK fusion protein, resulting from a 
chromosomal rearrangement frequently associated with anaplastic large cell 
lymphomas. The native ALK protein is normally expressed in the developing and, 
at a weaker level, adult nervous system. We recently demonstrated that ALK is a 
novel dependence receptor. As such, in the absence of ligand, the ALK receptor 
is kinase inactive and its expression results in enhanced apoptosis, whereas 
kinase activation, due to a ligand or constitutive as in NPM-ALK, decreases 
apoptosis. Unligated/kinase unactivated ALK receptor facilitates apoptosis via 
its own cleavage by caspases, a phenomenon allowing the exposure of a 
proapoptotic juxta-membrane intra-cellular domain. This review summarizes the 
biological significance of the ALK receptor in cancer and development, in 
perspective with its dependence receptor function. The dual function of ALK in 
the physiology of development is illustrated in the visual system of Drosophila. 
In this part of the nervous system, ALK in the presence of ligand appears 
essential for axonal guidance, whereas in the absence of ligand, ALK expression 
can lead to developmental neuronal apoptosis. ALK is also found expressed in 
neural crest-derived tumors such as human neuroblastomas or glioblastomas but 
its role is not fully elucidated. However, an excessive or constitutive ALK 
tyrosine kinase activation can lead to deregulation of cell proliferation and 
survival, therefore to human cancers such as lymphomas and inflammatory 
myofibroblastic tumors. Our observations could have important implications in 
the therapy of ALK-positive tumors harboring the chimeric or wild type ALK 
protein.