MINPP1, the multiple inositol-polyphosphate phosphatase 1 gene, is crucial for regulating inositol polyphosphate metabolism. Inositol polyphosphates are key metabolic and secondary messengers involved in diverse cellular functions like calcium homeostasis, cell survival, and death [1,3,4,5,6,7]. MINPP1, an endoplasmic reticulum (ER)-resident enzyme, hydrolyzes inositol phosphates, maintaining a proper balance of these molecules in the cell [2,3,5,6,7].

In Minpp1-deficient mice, levels of inositol 1,3,4,5,6-pentakisphosphate (InsP(5)) and inositol hexakisphosphate (InsP(6)) were 30-45% higher than in wild-type cells, indicating that ER-based Minpp1 is important for maintaining the steady-state levels of these polyphosphates [6]. In human patients, loss-of-function mutations in MINPP1 cause a distinct type of Pontocerebellar Hypoplasia, associated with an intracellular imbalance of inositol polyphosphate metabolism, specifically an accumulation of inositol hexakisphosphate (IP6) [1,2]. Patient-derived and genome-edited MINPP1-/-induced stem cells show inefficient neuronal differentiation and increased cell death [1].

In conclusion, MINPP1 plays a vital role in regulating inositol polyphosphate metabolism, which is essential for normal cell growth and brain development. The study of Minpp1-deficient mouse models and human patients with MINPP1 mutations has provided insights into its function in maintaining cellular homeostasis and its role in Pontocerebellar Hypoplasia.