Inorganic pyrophosphatase (human cytosolic isoform, PPA1) (PPase (for the general enzyme); In humans, the canonical gene symbol is PPA1)

Inorganic pyrophosphatase (PPase) is an enzyme found in all domains of life, catalyzing the hydrolysis of inorganic pyrophosphate (PPi) into two orthophosphate (Pi) ions, a reaction essential for driving many biosynthetic processes to completion. In humans, two major isoforms exist: PPA1 (cytosolic/housekeeping) and PPA2 (mitochondrial). PPA1 is essential for growth, metabolism, and development, and is upregulated in multiple cancer types, supporting cell proliferation, migration, and survival. Apart from its core metabolic function, PPA1 can dephosphorylate JNK1, linking it to cell signaling pathways relevant to oncogenesis. Inhibitors of PPase are being explored as anti-cancer and anti-parasitic agents. Safety concerns stem from the enzyme's universality and fundamental metabolic role, necessitating selective targeting for therapeutic purposes. No clinically approved drugs or treatments directly modulate human PPase yet, but experimental inhibitors are under study.

Other names

Inorganic diphosphatasePPasePyrophosphatase(human cytosolic isoform: PPA1)Sometimes distinguished as membrane pyrophosphatase, soluble pyrophosphatase or cytosolic pyrophosphatase, but these are subtypes/families

Direct enzymatic inhibition to reduce PPi hydrolysis, leading to accumulation and cellular metabolic disruption. In cancer, inhibition of PPA1 promotes apoptosis and reduces proliferation. In parasites, disruption of PPase impairs energy balance and survival.