CBLN1 encodes cerebellin-1 precursor, a synaptic organizer protein belonging to the C1q family that plays a crucial role in synapse formation and maintenance. The protein is produced and secreted from cerebellar granule cells and functions as a bidirectional synaptic organizer between Purkinje cells and parallel fibers 1. CBLN1 operates through a tripartite complex mechanism, where it binds to presynaptic neurexins and postsynaptic glutamate receptor δ2 (GluD2), forming a NRX/Cbln1/GluD2 complex that is resistant to low extracellular calcium levels 1. This complex serves as the missing ligand for the orphan receptor GluD2, establishing a direct ligand-receptor relationship 2. Loss of CBLN1 function causes severe cerebellar ataxia due to dramatic reduction in parallel fiber-Purkinje cell synapses, demonstrating its essential role in cerebellar synaptogenesis 2. Beyond excitatory synapse formation, CBLN1 also regulates the excitatory-inhibitory balance by suppressing inhibitory synapse formation between Purkinje cells and molecular layer interneurons 3. The protein has shown therapeutic potential, with synthetic versions successfully restoring synaptic functions and motor coordination in mouse models of cerebellar ataxia and other neurological disorders 4. Additionally, D-serine can disrupt CBLN1-GluD1 interactions, affecting synaptic function and nociceptive responses 5.