In considering how PLC activity may relate to migraine and its comorbidities, many of these distinct conditions share a multifaceted pathophysiology, with alterations in molecules as diverse as serotonin, adrenaline, estrogen, cannabinoids, and glutamate, and include the activation of several GPCRs, protein kinase mediated signaling, and early gene activation (c-fos) [36,37]. The gene discussed is HSPG2; the disease is migraine disorder.