Serine protease HTRA2, mitochondrial (HtrA2) is a serine protease that shows proteolytic activity against a non-specific substrate beta-casein. HtrA2 promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. HtrA2 cleaves THAP5 and promotes its degradation during apoptosis. Defects in HtrA2 are the cause of Parkinson disease type 13 (PARK13), a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins) in surviving neurons in various areas of the brain.

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