Cerebellin (CER), which was originally isolated from rat cerebellum, is a hexadecapeptide derived from a larger precursor Cerebellin 1, also designated precerebellin 1 or Cbln1. Four propeptides, Cerebellin 1, Cerebellin 2 (Cbln2), Cerebellin 3 (Cbln3), and Cerebellin 4 (Cbln4), comprise the precerebellin subfamily within the C1q protein family. Cerebellin family members act as transneuronal regulators of synapse development and synaptic plasticity in various brain regions. CER and it metabolite des-Ser1-cerebellin are also expressed in several extra-cerebellar tissues, including adrenal gland. Cerebellin 1, 2 and 3 assemble into homomeric and heteromeric complexes, thereby influencing each other’s degradation and secretion. Cerebellin 3 is not able to form homomeric complexes, and can only be secreted upon forming a heteromeric complex with Cerebellin 1. Decreased concentrations of CER has been found in the brain of patients with olivopontocerebellar atrophy (OPCA) and Shy-Drager syndrome, suggesting a role for CER in the pathology of these diseases.