This review commemorates the 10-year anniversary of the discovery of physiological ligands Augα (Augmentor α; ALKAL2; Fam150b) and Augβ (Augmentor β; ALKAL1; Fam150a) for anaplastic lymphoma kinase (ALK) and leukocyte tyrosine kinase (LTK), previously considered orphan receptors. This manuscript provides an in-depth review of the biophysical and cellular properties of ALK family receptors and their roles in cancer, metabolism, pain, ophthalmology, pigmentation, central nervous system (CNS) function, and reproduction. ALK and LTK receptors are implicated in the development of numerous cancers, and targeted inhibition of their signaling pathways can offer therapeutic benefits.
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