Abstract: Nuclear receptor subfamily 2 group F member 1 (NR2F1, also called COUP-TF1) is a transcription factor and part of the steroid/thyroid hormone receptor superfamily (Gay et al., 2002). NR2F1 is an orphan receptor that dimerizes to bind DNA and acts as a repressor as well as an activator of the target genes (Gay et al., 2002; Bertacchi et al., 2019; Bonzano et al., 2023). It was found recently to regulate the transcription of mitochondrial genes and to affect the morphology and mass of mitochondria (Bonzano et al., 2023). NR2F1 is mainly known for its pleiotropic role in neurodevelopment, but it has recently been connected to neurodegeneration in the context of Parkinson’s disease (PD) (Walter et al., 2021). This perspective summarizes the known functions of NR2F1 and offers a new perspective on its potential role in neurodegeneration.