ADPRHL1 (ADP-ribosylhydrolase like 1) is a cardiac-restricted pseudoenzyme essential for heart chamber development and myofibrillogenesis. Despite lacking catalytic activity against ADP-ribose substrates 1, ADPRHL1 functions through its substrate-binding cleft, particularly a di-arginine motif at the ancestral ADP-ribosylhydrolase site 2. The protein localizes to Z-disc boundaries of muscle actin filaments, where it regulates sarcomere assembly and cardiac chamber outgrowth during development 1. Loss-of-function mutations in ADPRHL1 impair myofibril assembly and ventricle growth 2. Beyond cardiac development, ADPRHL1 has broader disease relevance. A recurrent germline mutation (p.D78V) in African American families promotes prostate cancer through aberrant PARP1 activation, while wild-type ADPRHL1 functions as a tumor suppressor, with expression decreasing as Gleason scores increase 3. ADPRHL1 is associated with cardiac age acceleration 4 and has been identified as a prognostic marker in uveal melanoma 5 and hepatocellular carcinoma 6. Additionally, ADPRHL1 polymorphisms influence poultry growth and meat quality traits 7, suggesting evolutionary conservation of its growth-regulatory functions.