KO mice were used as a model to demonstrate that GalNAc-T2 co-regulates the metalloproteinase-mediated limited proteolysis of β1AR; aberrant O-glycosylation seems to enhance proteolysis allowing for receptor signaling attenuation (Goth et al., 2017), β1ARs contain an O-glycan-regulated ADAM17-dependent N-terminal cleavage site at S41↓L42 (Park et al., 2017), the β1AR signaling pathway emerges as a key actor during the progression of heart failure. Here, ADRB1 is linked to heart failure.