Mitochondria serve as the central hub of cellular energy metabolism. Beyond generating ATP via oxidative phosphorylation to sustain vital activities, they participate in regulating material metabolism, apoptosis, signal transduction, and reactive oxygen species homeostasis. Maintenance of mitochondrial homeostasis is indispensable for preserving intracellular microenvironmental stability and the physiological function of organs. LON protease 1 (LONP1) is an ATP-dependent protease encoded by the nuclear gene LONP1 (PRSS15), which is highly conserved and involved in various biological functions. LONP1, located in the mitochondrial matrix, plays a key role in maintaining mitochondrial homeostasis and protein quality control and participates in removing misfolded and oxidative modified protein, binding mitochondrial DNA (mtDNA), and being a molecular chaperone. To date, there is growing evidence that LONP1, through its regulation of mitochondrial quality and energy homeostasis, is involved in development, aging, and various diseases. This article will review the biological characteristics, structure, and function of LONP1, as well as the advances of LONP1 in embryonic development, aging, cancer, and various diseases.