Cerebellin1

Cerebellin-1, abbreviated as CBLN1, is a secreted glycoprotein belonging to the cerebellin family and encoded by the CBLN1 gene. It is expressed predominantly by cerebellar granule cells in the mammalian brain and is released into the synaptic cleft where it functions as a synaptic organizer. CBLN1 contains a C1q-like domain and forms multimeric assemblies, typically hexamers, which are thought to be important for receptor engagement and signaling at synapses.

In terms of function, CBLN1 contributes to the formation and maintenance of glutamatergic synapses between granule cell parallel fibers and Purkinje cells. It promotes the assembly of a trans-synaptic signaling complex by engaging presynaptic neurexins (NRXN) and the postsynaptic GRID2 (glutamate receptor delta-2) on Purkinje cells. This CBLN1-centered complex is believed to help organize synaptic contacts and stabilize connections within the cerebellar circuitry.

Genetic disruption of CBLN1 in mice leads to a reduction of parallel fiber–Purkinje cell synapses and cerebellar dysfunction, often presenting as ataxia. The phenotype underscores CBLN1’s role in cerebellar development and synapse maintenance. Some rescue experiments support a direct, cell-autonomous role for CBLN1 in sustaining synaptic structure and function.

CBLN1 is part of a small cerebellin gene family (CBLN1-4) with overlapping expression patterns and functions across the brain. Beyond the cerebellum, ongoing research investigates how cerebellin signaling contributes to broader aspects of synapse organization and its relevance to neurological disorders.