PHLPP1, short for PH domain Leucine-rich repeat Protein Phosphatase 1, is a Ser/Thr phosphatase. It plays a crucial role in multiple biological processes by regulating various signaling pathways. It is involved in mitochondrial homeostasis, inflammatory signaling, extracellular matrix regulation, and lipid metabolism [1,2,3,6]. Genetic models, especially gene knockout (KO) and conditional knockout (CKO) mouse models, have been valuable in studying its functions.

In KO mouse models, Phlpp1 deficiency protected against age-related intervertebral disc degeneration by promoting beneficial phenotypic changes and reducing extracellular matrix degradation and cell apoptosis, potentially through FOXO1 activation [3]. In cardiomyocytes, conditional PHLPP1 deficiency alleviated myocardial ischemic injury and doxorubicin-induced myocardial injury, improving cardiac function by inhibiting Mcl-1 degradation [4]. In osteoblasts, deletion of Phlpp1 in type 1 collagen-expressing cells did not significantly change peak bone mass but enhanced inflammatory gene expression and the RANKL/OPG ratio [5].

In conclusion, PHLPP1 is essential in regulating mitochondrial homeostasis, inflammation, extracellular matrix-related processes, and lipid metabolism. KO and CKO mouse models have revealed its significance in diseases such as intervertebral disc degeneration, cardiac diseases, and potentially in bone-related conditions, providing insights into disease mechanisms and potential therapeutic targets.