α1-Syntrophin is a component of the dystrophin scaffold-protein complex that acts in recruiting proteins through their multiple protein–protein interaction motifs to the cytoplasmic side of plasma membranes. Proteins interacting with α1-syntrophin include voltage-gated sodium channels, neuronal nitric oxide synthase, calmodulin, ankyrin repeat-rich membrane spanning protein, G-proteins and more. 

The syntrophin family comprises five members: α1-syntrophin, β1-syntrophin, β2-syntrophin, γ1-syntrophin, and γ2-syntrophin¹.

α1-Syntrophin is a peripheral cytoplasmic membrane protein in skeletal and cardiac muscle cells¹.

The α1-syntrophin structure contains four conserved domains, two pleckstrin homology domains (PH1 and PH2), a PSD95-disks large-ZO1 (PDZ) domain and a syntrophin unique (SU) COOH-terminal domain². The pleckstrin domains are responsible for the recruitment of proteins to the sarcolemma. The PDZ domain is inserted within the PH1 domain and binds to NOS-1 in skeletal muscle. This domain also binds to the C-terminus of the K_ir2.1 channel and also to Na_V1.5 and so allowing them to interact. The SU domain binds syntrophin to dystrophin^2,3. α1-Syntrophin is also responsible for the site-specific anchoring of AQP4 protein. α1-Syntrophin deletion leads to the disruption of the polarized subcellular expression of AQP4 in the perivascular membranes⁴. 

Several studies have shown that syntrophin-deficiency in Duchenne muscular dystrophy can ultimately lead to muscle degeneration. Syntrophin-deficiency was also shown to reduce levels of nNOS in mice^5,6.