[8][9] Since the original discovery of the receptor in mammals, several orthologs of ALK have been identified: dAlk in the fruit fly (Drosophila melanogaster) in 2001,[10] scd-2 in the nematode (Caenorhabditis elegans) in 2004,[11] and DrAlk in the zebrafish (Danio rerio) in 2013.

[12] The ligands of the human ALK/LTK receptors were identified in 2014:[13][14][15] FAM150A (AUGβ) and FAM150B (AUGα), two small secreted peptides that strongly activate ALK signaling.

ALK phosphorylated residues serve as binding sites for the recruitment of several adaptor and other cellular proteins, such as GRB2,[20] IRS1,[20][21] Shc,[20][22] Src,[23] FRS2,[22] PTPN11/Shp2,[24] PLCγ,[25][21] PI3K,[26][21] and NF1.

[36] Phosphorylated ALK activates multiple downstream signal transduction pathways, including MAPK-ERK, PI3K-AKT, PLCγ, CRKL-C3G, and JAK-STAT.

[37][19] The receptor ALK plays a pivotal role in cellular communication and in the normal development and function of the nervous system.

[6] This observation is based on the extensive expression of ALK messenger RNA (mRNA) throughout the nervous system during mouse embryogenesis.

Flies lacking the receptor die due to failure of founder cell specification in embryonic visceral muscle.

[43][44][45] ALK regulates retinal axon targeting,[46] growth and size,[27][47] synapse development[11] at the neuromuscular junction,[48][49] behavioral responses to ethanol,[50][51][52][53] and sleep.

[60] The standard test used to detect this gene in tumor samples is fluorescence in situ hybridization (FISH) by a US FDA approved kit.