OARD1 (O-acyl-ADP-ribose deacylase 1) is an ADP-ribose glycohydrolase that functions as a key regulator of ADP-ribosylation signaling by removing ADP-ribose modifications from proteins. The enzyme specifically acts as a glutamate mono-ADP-ribosylhydrolase, mediating the removal of mono-ADP-ribose attached to glutamate residues on proteins, but cannot directly process poly-ADP-ribosylated proteins 1. OARD1 also catalyzes the deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose, and O-butyryl-ADP-ribose, yielding ADP-ribose plus the corresponding organic acids. The enzyme's mechanism involves hydrolysis of ADP-ribose linkages and acts on substrates that have been processed by other enzymes like PARG 1. OARD1 has emerging clinical relevance, as genetic variants in the OARD1/NFYA/TREML1 genomic region are significantly associated with Alzheimer's disease risk 23. Additionally, OARD1 variants show associations with diabetic retinopathy through shared genetic pathways with Alzheimer's disease 4, and with Kashin-Beck disease, an endemic osteoarthritis-like condition 5. OARD1 also demonstrates responsiveness to metabolic changes, with expression levels positively correlating with insulin sensitivity in human skeletal muscle 6. These associations suggest OARD1 plays important roles in neurodegeneration, metabolic regulation, and cartilage homeostasis.