CASK, which belongs to the family of membrane-associated guanylate kinase 
(MAGUK) proteins, is recognized as a multidomain scaffolding protein highly 
expressed in the mammalian nervous system. MAGUK proteins generally target to 
neuronal synapses and regulate trafficking, targeting, and signaling of ion 
channels. However, CASK is a unique MAGUK protein in several respects. It not 
only plays a role in synaptic protein targeting but also contributes to neural 
development and regulation of gene expression. Several CASK-interacting proteins 
have been identified from yeast two-hybrid screening and biochemical isolation. 
These proteins, whose interactions with CASK are reviewed here, include the 
Parkinson's disease molecule parkin, the adhesion molecule neurexin, syndecans, 
calcium channel proteins, the cytoplasmic adaptor protein Mint1, 
Veli/mLIN-7/MALS, SAP97, caskin and CIP98, transcription factor Tbr-1, and 
nucleosome assembly protein CINAP. More important, CASK may form different 
complexes with different binding partners and perform different functions. Among 
these interactions, CASK, Tbr-1, and CINAP can form a transcriptional complex 
regulating gene expression. Reelin and NMDAR subunit 2b (NR2b) genes have been 
identified as Tbr-1 target genes. Reelin is critical for neural development. 
NR2b is an important subunit of NMDAR, which plays important roles in neural 
function and neurological diseases. Regulation of reelin and NR2b expression 
suggests the potential roles of the Tbr-1-CASK-CINAP complex in neural activity, 
development, and disease. The functions of these CASK protein complexes are also 
discussed in detail in this review.