C1QL2 (complement C1q-like 2) is a synaptic organizer protein that regulates excitatory synapse formation and function in the hippocampus, particularly at mossy fiber-CA3 synapses 1. As a secreted extracellular molecule, C1QL2 recruits postsynaptic kainate receptors (KARs) to CA3 pyramidal neurons by binding their amino-terminal domains and interacting with presynaptic neurexin-3 (Nrxn3), thereby organizing the postsynaptic complex 1. This function is controlled by the transcription factor Bcl11b, which directly targets C1ql2 expression to regulate synaptic vesicle recruitment and long-term potentiation at mossy fiber-CA3 synapses 2. C1QL2 specifically modulates KAR-mediated slow channel kinetics and does not affect inhibitory synapses. In pathological contexts, C1ql2/C1ql3 double-null mice fail to recruit KARs postsynaptically even with mossy fiber sprouting, reducing recurrent circuit activity and suggesting antiepileptic potential 1. Beyond CNS function, elevated plasma C1QL2 serves as a diagnostic biomarker for primary biliary cholangitis 3, and C1QL2 (also termed CTRP10) regulates body weight in a sexually dimorphic manner 4. C1QL2 dysfunction links to cocaine addiction pathways 5 and predicts loss of HIV viral control 6, indicating broader involvement in synaptic plasticity and systemic homeostasis.