Through the use of all the available P2Y12-immunoreactive antibodies recognizing the C-terminus or the second intracellular loop of the receptor, the aim of the present work is to provide comparative evidence about P2Y12 cell specificity in microglia versus oligodendrocytes particularly from the healthy and diseased CNS under neuroinflammatory conditions as those sustained during amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Here, P2RY12 is linked to amyotrophic lateral sclerosis.