ART5 (ADP-ribosyltransferase 5) is a mono-ADP-ribosyltransferase that catalyzes the transfer of ADP-ribose from NAD to arginine residues on target proteins 1. Unlike its paralogues ART1 and ART2, ART5 lacks a glycosylphosphatidylinositol-anchor signal sequence and functions as a secretory enzyme 2. The protein exhibits NAD-glycohydrolase activity 2 and is prominently expressed in testis with lower levels in cardiac and skeletal muscle 2. ART5 shares 87% sequence identity with its human orthologue 2. Mechanistically, ART5 participates in protein post-translational modification through ADP-ribosylation, a reversible modification that can be reversed by ADP-ribosylarginine hydrolases 3. The enzyme contains conserved catalytic domains for NAD binding and ADP-ribose transfer 1. In disease contexts, ART5 expression is significantly downregulated as an early signature of parathyroid hyperplasia, with loss of ART5 expression associated with parathyroid tumorigenesis 4. In castration-resistant prostate cancer, ART5 is recruited by the oncogenic lncRNA FALEC to enhance PARP1-mediated self-PARylation, and ART5 downregulation decreases CRPC cell viability 5. These findings suggest ART5 may serve as both a biomarker and therapeutic target in cancer progression.