N-Phosphorylation, pLys (Phospholysine) and pHis (Phosphohistidine) is one of the most frequent PTM (Post-translational modification) and has an important role as the controller of cell signaling and metabolism. Especially, LHPP (Phospholysine Phosphohistidine Inorganic Pyrophosphatase) is well known for a tumor suppressor but still, its mechanism is uncharted territory. Researching for specific substrate and activator of LHPP might pioneer the novel anticancer drug target. Investigation of LHPP through high-throughput screening for activator and substrate might be helpful of elucidating of LHPP’s mechanism.