Finally, knocking down E2f4 using an E2f4-specific shRNA significantly decreased the protein levels of p-ERK [35], a key MAPK that has been involved in both neurodegenerative diseases, as well as in endocannabinoid [123,124,125,126,127,128] and calcium signaling [101,105,129,130,131,132,133], which are critical pathways in synaptic function and modulation. The gene discussed is E2F4; the disease is neurodegenerative disease.