Phpt1, also known as Phosphohistidine phosphatase 1, is an enzyme that regulates phosphohistidine levels of several proteins involved in signaling, lipid metabolism, and potassium ion transport. It is the only known phosphohistidine phosphatase in mammals and has been implicated in multiple cellular signaling pathways [3,4].

In lung cancer, Phpt1 is overexpressed and correlates with poor overall survival. Inhibition of its expression in EGFR-mutant lung cancer cells decreases their proliferation, clonogenicity, and in vitro tumor growth. It also drives activation of the ERK/MAPK pathway and is required for maintaining drug resistance to erlotinib in these cells. FBXO32 acts as an E3 ubiquitin ligase for Phpt1, and its knockdown leads to Phpt1 accumulation, activation of the ERK/MAPK pathway, and promotion of lung cancer cell growth [1].

In brown adipocyte differentiation, the expression level of Phpt1 changes during the process. Knockdown of Phpt1 promotes brown adipocyte differentiation, while its ectopic expression suppresses it, suggesting a link between histidine phosphorylation and brown adipocyte differentiation [2].

In conclusion, Phpt1 is crucial in regulating various biological processes such as cell growth in lung cancer and brown adipocyte differentiation. Its overexpression in lung cancer and its role in drug resistance make it a potential biomarker and therapeutic target. The study of Phpt1 using loss-of-function models has provided insights into its role in these disease-related biological processes.