PTPMT1, a mitochondrial tyrosine phosphatase, is essential for de novo cardiolipin biosynthesis in mitochondria [1]. Cardiolipin, mainly located in the inner mitochondrial membrane, is fundamental to mitochondrial biology, and thus PTPMT1 is involved in maintaining normal mitochondrial structure and function, which is crucial for various biological processes [1]. Genetic models, such as knockout zebrafish and RNA interference-mediated knockdown in insects, have been used to study its functions [1,4,5].

In humans, biallelic variants in PTPMT1 disrupt cardiolipin metabolism, leading to a neonatal/infantile onset neurological and neurodevelopmental syndrome, including developmental delay, microcephaly, and more [1]. In zebrafish, ptpmt1 knockout causes abnormalities in body size, development, decreased total cardiolipin levels, and OXPHOS deficiency [1]. In the red flour beetle, PTPMT1-knockdown larvae show a prolonged larval period and reduced expression of mitochondrial genome-encoded genes [5]. In induced pluripotent stem cell-derived cardiomyocytes and rat H9C2 cells, γ-ray irradiation decreases PTPMT1 expression, while overexpression of PTPMT1 can protect cardiomyocytes from necroptosis induced by γ-ray irradiation by alleviating mitochondrial injury [2]. In pancreatic cancer cells, PTPMT1 silencing reduces cell viability and causes mitochondrial damage, and it may modulate mitochondrial function via the SLC25A6-NDUFS2 axis [3].

In conclusion, PTPMT1 plays a vital role in maintaining mitochondrial function through regulating cardiolipin metabolism and other related pathways. Studies using gene knockout or knockdown models have revealed its significance in neurodevelopment, cardiovascular function, and cancer biology, providing insights into the underlying mechanisms of related diseases and potential therapeutic targets [1,2,3,5].