Syntrophins are a family of five membrane associated adaptor proteins with a molecular weight of 58-60 kDa. Adaptor proteins play a crucial role in coordinating signaling events and may act as rescuers in situations where a subversion from normal signaling exists. Syntrophins are characterized by the presence of a PDZ (postsynaptic density protein-95/disc large/zona occludens-1) split PH (pleckstrin homology) domain and a SU (syntrophin unique) domain within their structure.

β-1 Syntrophin is a 538 amino acid long protein while β-2 is 540 amino acid in length. Both forms are ubiquitously expressed in mammalian tissues however β-1 is the predominant form. β-1 Syntrophin is the basic form of the protein while α-1 is acidic. Like all forms of syntrophin, β-1 syntrophin may exist as a monomer or dimer within the cell. Almost all isoforms of syntrophin bind to each other.

Syntrophin is required for the proper localization expression and function of Na_V1.4 and Na_V1.5 Na⁺ channels. Both channels take part of a multi-protein complex in which dystrophin and syntrophin proteins play an important role in determining their expression levels. Na_V1.4 and Na_V1.5 C-termini consist of the PDZ domain-binding motif formed by the last three residues. The C-terminus of Na_V1.5 thus binds with the dystrophin of DGC and this interaction is mediated by and β-syntrophin (and α-syntrophin) proteins¹.

Syntrophin binds directly to dystrophin at the vicinity of dystrophin’s GPC binding site. Another low affinity binding site is presumed to exist at the COOH-terminal region of dystrophin².