Although accumulating data suggests that C3 and C1QA regulation might be the target of mitigating microglia toxicity and neurodegeneration, no therapeutic effect was observed in C1Q, or C3 gene deleted SOD1G37R mice model (Lobsiger et al., 2013; Zhang et al., 2020), which demonstrated that activating a complement pathway containing C1Q and C3 might not be the major part of ALS pathogenesis in mice. The gene discussed is C3; the disease is amyotrophic lateral sclerosis.