Liprin-alpha-4 is a member of the LAR (leukocyte common antigen-related) protein tyrosine phosphatase-interacting protein (liprin) family []. Liprin-alpha family proteins in mammals are expressed at high levels in the brain and are engaged in high-affinity interactions with many presynaptic active zone proteins []. Liprin-alpha-4 is most abundant at parallel fibre-Purkinje cell synapses in the molecular layer of the hippocampus []. Liprin was originally identified as binding partners of the receptor protein tyrosine phosphatase LAR (leukocyte common antigen-related), which functions inaxon guidance and mammary gland development []. In vertebrates, there are two families of liprins, liprin-alpha and liprin-beta, which have four (alpha1-4) and two (beta1-2) members. Liprins contain an N-terminal coiled-coil domain and a C-terminal liprin homology (LH) region comprised of three sterile alpha motif (SAM) domains. The N-terminal coiled coils of liprin-alpha act as binding regions for several synaptic protein, while the SAM repeats can bind to both phosphatases and protein kinases []. The autophosphorylation of liprin regulates its association with LAR []. Interestingly, all Liprin-alpha genes are subject to alternative splicing, which is regulated in a developmental manner []. The structure of the human CASK/liprin-alpha/liprin-beta ternary complex has been revealed [].
