SynCAMs are a family of 4 proteins (SynCAM1-4) belonging to the immunoglobulin superfamily of cell adhesion molecules (IgCAMs) and are encoded by the cell adhesion molecule 1-4 (CADM1-4) genes^1-3.

Evolutionarily, SynCAMs are a fairly recent gene lineage since they are only found in vertebrates¹, in contrast to much older synaptogenic adhesion molecules such as neuroligins, which appeared concurrently with the evolution of the first synapses around one billion years ago, or compared to even older protosynaptic adhesion molecules including neurexins and NCAM⁴.

CADM1 (also known as SynCAM1), by far the most studied family member, was identified nearly simultaneously in multiple tissue types and therefore is known by a number of different protein names including immunoglobulin subfamily member 4 (IGSF4)⁵, spermatogenic immunoglobulin superfamily (SgIGSF)⁶, and RA175⁷.

CADM1 was also initially discovered as a tumor suppressor gene and termed tumor suppressor in non-small cell lung cancer (TSLC1)⁸. In fact, CADM1 is downregulated in several tumors including lung, ovarian, hepatocellular carcinoma and glioblastoma, and has been proposed as both a biomarker of malignancy and a therapeutic target⁹.

In addition, CADM1 knockout mice have impaired ultrasonic vocalization, a method for mother-offspring communication, which supports a role for CADM1 in autism spectrum disorders (ASD)¹⁰.