In addition, deregulated parkin (PRKN) expression and/or activity is pathognomonic to PD, however, parkin-interacting substrate (PARIS/ZNF746), a Krüppel-associated box-zinc finger protein (KRAB-ZFP) that accumulates in models of parkin (PRKN) inactivation and in the brain of patients with PD, has been shown to repress the expression of PGC-1α and its substrate, the nuclear respiratory factor (NRF)-1, by targeting insulin response sequences in the promoter regions of PGC-1α [48]. The gene discussed is PPARGC1A; the disease is Parkinson disease.