Syntrophins are a family of cytoplasmic membrane-associated adaptor
proteins, characterized by the presence of a unique domain organization comprised of a C-terminal
syntrophin unique (SU) domain and an N-terminal
pleckstrin homology (PH) domain that is split by insertion of a PDZ domain. Syntrophins have been recognized as an important component of many signaling events, and they seem to function more like the cell's own personal 'Santa Claus' that serves to 'gift' various signaling complexes with precise
proteins that they 'wish for', and at the same time care enough for the spatial, temporal control of these signaling events, maintaining overall smooth functioning and general happiness of the cell. Syntrophins not only associate various
ion channels and signaling
proteins to the
dystrophin-associated protein complex (
DAPC), via a direct interaction with
dystrophin protein but also serve as a link between the extracellular matrix and the intracellular downstream targets and cell cytoskeleton by interacting with
F-actin. They play an important role in regulating the postsynaptic signal transduction, sarcolemmal localization of nNOS, EphA4 signaling at the neuromuscular junction, and
G-protein mediated signaling. In our previous work, we reported a differential expression pattern of alpha-1-syntrophin (SNTA1)
protein in esophageal and
breast carcinomas. Implicated in several other pathologies, like cardiac dys-functioning,
muscular dystrophies, diabetes, etc., these
proteins provide a lot of scope for further studies. The present review focuses on the role of syntrophins in membrane targeting and regulation of cellular
proteins, while highlighting their relevance in possible development and/or progression of pathologies including
cancer which we have recently demonstrated.