AMIGO2 (amphoterin‑induced gene and ORF 2), also known as DEGA and Alivin‑1, is an approximately 65 kDa transmembrane cell adhesion protein. It belongs to a family of leucine‑rich repeat (LRR) containing proteins that play various roles in nervous system development and function (1, 2). Mature mouse AMIGO2 consists of a 359 amino acid (aa) extracellular domain (ECD) with six LRRs flanked by single LRRNT and LRRCT domains, followed by one immunoglobulin-like domain, a 21 aa transmembrane segment, and a 101 aa cytoplasmic domain (3-5). Within the ECD, mouse AMIGO2 shares 89% and 94% aa sequence identity with human and rat AMIGO2, respectively. AMIGO2 forms homodimers as well as heterodimers with the related AMIGO1 and AMIGO3 molecules (3, 6). Within the nervous system, AMIGO2 is transcribed in the cerebrum, hypothalamus, olfactory bulb, retina, hippocampus (pyramidal cells), and cerebellum (granule neurons and Purkinje cells) (3, 4, 7). It is also expressed in the liver, lung, testis, spleen, and small intestine (3, 4). AMIGO2 supports neuron survival, and is down-regulated following pro‑apoptotic stimulation (4). Its expression can be up‑regulated or down-regulated in a variety of cancers, and anti‑sense knockdown of AMIGO2 interferes with tumor cell adhesion to collagen as well as in vivo tumorigenicity (5). AMIGO2 modulates T cell functions and its deficiency in mice ameliorates experimental autoimmune encephalomyelitis (6).