Pyrroline-5-carboxylate reductase 2 (PYCR2)

Pyrroline-5-carboxylate reductase 2 (PYCR2) is a mitochondrial oxidoreductase enzyme that catalyzes the final step in cellular L-proline biosynthesis: the NAD(P)H-dependent reduction of Δ^1^-pyrroline-5-carboxylate (P5C) to L-proline. There are three human isoforms (PYCR1, PYCR2, PYCR3), with PYCR2 specifically localized to mitochondria. PYCR2 plays a critical role in maintaining cellular redox homeostasis and normal mitochondrial function. Pathogenic mutations in PYCR2, such as Arg119Cys and Arg251Cys, lead to drastically reduced enzyme activity and are causative for hypomyelinating leukodystrophy type 10 and related neurodevelopmental disorders. Structural studies have characterized catalytic and folding defects associated with these variants. Despite its therapeutic relevance in rare diseases, PYCR2 is not a current direct drug target but may be considered for future pharmacological or genetic intervention in metabolic and neurodevelopmental pathologies.

Other names

PYCR2P5C reductase 2P5CR 2P5CR2HLD10Pyrroline-5-carboxylate reductase family member 2

Enzyme inhibition (hypothetical for drugs): Inhibition of PYCR2 would lead to decreased proline biosynthesis and altered cellular redox balance.