Although several protein families have four transmembrane alpha-helices, tetraspanins are defined by conserved amino acid sequences including four or more cysteine residues in the EC2 domain, with two in a highly conserved 'CCG' motif.

Some tetraspanins can have N-linked glycosylations on the long extracellular loop (LEL, EC2) and palmitoylations at a CXXC motif in their transmembrane region.

Tetraspanins display numerous properties that indicate their physiological importance in cell adhesion, motility, activation, and proliferation, as well as their contribution to pathological conditions such as metastasis or viral infection.

it is hypothesized that tetraspanins interact with and regulate other platelet receptors.

TSP-2 antibodies are found in some people who seem to have immunity to schistosome infection (Schistosomiasis).