LONP2 is an ATP-dependent serine protease localized to the peroxisomal matrix that selectively degrades oxidatively damaged and misfolded proteins 1. As a key component of peroxisomal protein quality control, LONP2 facilitates the processing of peroxisomal targeting signal-containing proteins and supports peroxisomal matrix protein import 2. LONP2 functions to maintain peroxisomal proteostasis and metabolic capacity, particularly during long-chain fatty acid β-oxidation and in response to hydrogen peroxide generation, a byproduct of peroxisomal metabolism 12. Clinically, LONP2 dysregulation has emerged as a cancer-related factor. LONP2 expression is significantly upregulated in head and neck squamous cell carcinoma (HNSCC) and cervical cancer, where it promotes tumor cell proliferation, migration, and invasion 34. In HNSCC, LONP2 oncogenic effects operate via positive regulation of the actin-bundling protein PLS3 3. In cervical cancer, LONP2 promotes tumorigenesis through oxidative stress pathways 4. Conversely, LONP2 knockdown impairs cancer cell cycle progression and enhances apoptosis. Additionally, LONP2 appears under positive selection in East Asian populations, potentially reflecting dietary adaptation 5, and represents a component of fatty acid oxidation-related prognostic models in HNSCC 6.