PMPCA encodes the alpha subunit of mitochondrial processing peptidase (MPP), an essential enzyme responsible for cleaving mitochondrial targeting sequences from newly imported precursor proteins in the mitochondrial matrix 1. This protein processing function is crucial for the maturation of nuclear-encoded mitochondrial proteins necessary for cellular survival 1. Mutations in PMPCA cause spinocerebellar ataxia, autosomal recessive type 2 (SCAR2), characterized by non-progressive cerebellar ataxia and intellectual disability 1. The p.Ala377Thr mutation impairs both alpha subunit levels and MPP function, particularly affecting frataxin maturation, the protein depleted in Friedreich ataxia 1. More severe PMPCA variants can cause progressive developmental delay, cerebellar atrophy, and brain iron accumulation resembling neurodegeneration with brain iron accumulation (NBIA) 2. Recently, heterozygous PMPCA variants have been identified in dominant optic atrophy, where frameshift mutations reduce α-MPP levels and cause mitochondrial network hyperconnection, leading to retinal ganglion cell degeneration 3. The protein's dysfunction affects mitochondrial fusion-fission balance, highlighting its broader role beyond protein processing in maintaining mitochondrial network dynamics 3.