4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL)

4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) is a mitochondrial iron-dependent enzyme, structurally related to 4-hydroxyphenylpyruvate dioxygenase but with distinctive, yet incompletely characterized, activity. HPDL localizes to the mitochondrial intermembrane space and is implicated in regulating mitochondrial respiration and cellular ATP production through glutamine metabolism. It plays an essential role in maintaining redox balance via a glutamine-dependent antioxidant pathway, and protects against oxidative stress. HPDL overexpression is associated with pancreatic cancer progression and poorer outcomes, while biallelic mutations in HPDL result in neurodegenerative conditions such as hereditary spastic paraplegia (SPG83). Though its exact substrate and enzymatic products remain undefined, HPDL's function is critical for cellular metabolism, redox homeostasis, and potentially for neuronal integrity and cell survival in disease.

Other names

4-hydroxyphenylpyruvate dioxygenase-like proteinHPDLGLOXD1HPD-like proteinMGC156684-HPPD-Lglyoxalase domain-containing protein 1NEDSWMASPG83

Not established drug mechanisms, but molecular function involves mitochondrial bioenergetics regulation and redox balance, especially via glutamine metabolism.