CBLN3 (cerebellin 3 precursor) is a synaptic regulatory protein belonging to the cerebellin family of C1q proteins. CBLN3 is predominantly expressed in the cerebellum 1 and functions as a transneuronal regulator of synaptic integrity. Unlike CBLN1, CBLN3 is not secreted when expressed alone but is retained in the endoplasmic reticulum; however, it can be secreted when forming heteromeric complexes with other cerebellin family members, particularly CBLN1 2. This heteromerization may modulate trafficking and signaling pathways critical for synaptic function. CBLN3 serves as a marker of cerebellar Purkinje cell health, with expression levels significantly correlated with other Purkinje cell biomarkers (PCP2, PCP4) and reduced in Alzheimer's disease patients 3. The protein is involved in synaptic maintenance and trans-synaptic signaling. Disease relevance includes potential involvement in neurodegenerative conditions; CBLN3 was identified as a candidate biomarker in progressive supranuclear palsy cerebrospinal fluid 4 and has been implicated in hearing loss with vestibular abnormalities 5. Additionally, CBLN3 expression is altered during chr14 parasitic infection of the central nervous system 6. CBLN3 represents an important component of cerebellar synaptic architecture with potential clinical significance for diagnosing neurodegenerative and neurological disorders.