This is the case of OA, in which ADAM17 mediates the aberrant shedding of LRP1, a key protein that governs extracellular levels of the cartilage-degrading enzymes [117], or AD, in which ADAM17 may contribute to development of the disease by shedding LRP1 and TREM2, two proteins involved in the cellular disposal of Aβ peptide and amyloid plaques [111,150]. Here, LRP1 is linked to Alzheimer disease.