TNAP inhibitors constitute a diverse group of compounds that modulate the activity of tissue-nonspecific alkaline phosphatase (TNAP), either directly or indirectly. Levamisole, an alkaline phosphatase inhibitor, acts indirectly by interfering with the proper folding and maturation of TNAP, resulting in reduced enzyme activity. Similarly, lansoprazole, a proton pump inhibitor, indirectly impacts TNAP by altering intracellular pH, affecting the enzyme's conformation and function. Sodium orthovanadate, a phosphatase inhibitor, indirectly influences TNAP by modulating cellular phosphate levels through the inhibition of various phosphatases. Pyrophosphate, a substrate analog, competes with TNAP substrates, acting as a competitive inhibitor and reducing enzyme activity. Beta-glycerophosphate, another TNAP substrate analog, acts as a substrate mimic, enhancing TNAP activity by providing an alternative substrate.Ibandronate, a bisphosphonate, indirectly affects TNAP activity by influencing the availability of phosphate ions in the extracellular matrix during bone metabolism. Zinc chloride, a TNAP inhibitor, has been implicated in modulating TNAP activity, although the exact mechanism remains unclear. 5'-Methylthioadenosine, an endogenous metabolite, may influence TNAP activity by affecting cellular signaling pathways or metabolic processes. Menadione, a vitamin K analog, may modulate TNAP activity, although the specific mechanism is not well-defined. Phosphonoformic acid and zinc acetate are reported TNAP inhibitors, affecting enzyme activity by competing with substrates.