AbstractMembrane‐associated guanylate kinases (MAGUKs) are modular adapter proteins that serve as scaffolding molecules and anchor channels and receptors via their PDZ (PSD‐95, Dlg, Zo‐1) domains. Calcium, calmodulin‐associated serine/threonine kinase (CASK) is a MAGUK that is critical at synapses in the central nervous system and at cell–cell junctions because of its interactions with channels, receptors, and structural proteins. We show via confocal microscopy that CASK and another MAGUK, Discs Large (Dlg), are present at the mammalian neuromuscular junction in skeletal muscle. Immunoprecipitation data from mouse muscle show that CASK associates with Dlg, providing evidence of a MAGUK protein complex at this synapse. These data indicate that CASK and Dlg may act as a scaffold for organizing receptors and channels at the postsynaptic membrane of the neuromuscular junction. Muscle Nerve 30: 164–171, 2004