Complement C1q-like protein 3 (C1QL3)

Complement C1q-like protein 3 (C1QL3) is a secreted, trimeric glycoprotein highly expressed in the central nervous system, belonging to the C1q/TNF superfamily[2][6]. It acts as a synaptic organizer, modulating the formation, maintenance, and plasticity of excitatory synapses, and is involved in cell-cell adhesion complexes at neuronal synapses[1][3][4][5]. C1QL3 binds directly to the adhesion G protein-coupled receptor B3 (ADGRB3, also known as Brain-specific Angiogenesis Inhibitor 3 or BAI3), forming a unique trans-synaptic adhesion complex in excitatory neurons, and it can further interact with neuronal pentraxins such as NPTX1 and NPTXR[1][4]. Structurally, it forms stable homotrimers with distinctive Ca²⁺ binding in their C1q-like globular domains, enabling the clustering and organization of synaptic receptors such as BAI3[2][3]. Beyond the CNS, C1QL3 has pleiotropic roles, including regulation of glucose uptake in adipocytes, myotubes, and hepatocytes via the AMPK signaling pathway, implicating it in systemic metabolic homeostasis and potential involvement in diabetes mellitus[7]. Genetic variations or altered expression of C1QL3 have been linked to neurodevelopmental and metabolic disorders such as autism spectrum disorder and eating disorders[7][5]. No drugs currently target C1QL3 directly, and its complex involvement in both neural and metabolic signaling networks means that significant research is needed to evaluate druggability or safety of targeting this protein in therapeutic contexts.

Other names

Complement C1q-like protein 3C1QL3CTRP13C1q/TNF-related protein 13K100C1qlC1QTNF13complement component 1, q subcomponent-like 3