LAR-RPTPs: synaptic adhesion molecules that shape synapse development

•Both pre- and postsynaptic functions of LAR-RPTPs are concisely described.•Extracellular adhesion pathways mediated by LAR-RPTPs are extensively discussed.•Intracellular signaling pathways dictated by LAR-RPTPs are discussed in detail.•Diseases associated with dysfunctions of LAR-RPTP complexes are summarized.

The synapse is the most elementary operating unit in neurons, creating neural circuits that underlie all brain functions. Synaptic adhesion molecules initiate neuronal synapse connections, promote their stabilization and refinement, and control long-term synaptic plasticity. Leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) have previously been implicated as essential elements in central nervous system (CNS) development. Recent studies have demonstrated that LAR-RPTP family members are also involved in diverse synaptic functions, playing a role in synaptic adhesion pathways together with a host of distinct transmembrane proteins and serving as major synaptic adhesion molecules in governing pre- and postsynaptic development, dysfunctions of which may underlie various disorders. This review highlights the emerging role of LAR-RPTPs as synapse organizers in orchestrating synapse development.