LMF2 (lipase maturation factor 2) is an endoplasmic reticulum-resident protein involved in protein maturation and transport. While its primary characterized function relates to lipid metabolism—rare loss-of-function variants in LMF2 are associated with increased hepatic fat accumulation 1—LMF2 has emerged as a potential biomarker for neurodegenerative disease. DNA methylation levels in the NCAPH2/LMF2 promoter region are significantly decreased in Alzheimer's disease (AD) and amnesic mild cognitive impairment (aMCI) patients compared to controls 2, with methylation status showing associations with hippocampal atrophy in these populations 3. This epigenetic modification may influence disease progression through apoptotic mechanisms 3. The clinical significance of LMF2 methylation as a biomarker for early AD and aMCI diagnosis has been proposed 2, though clinical validation remains limited 4. Additionally, LMF2 copy number variations show associations with metabolic adaptation in sheep 5. However, mechanistic understanding of how LMF2 epigenetic or genetic alterations contribute to neurodegeneration remains incomplete, and further investigation is needed to establish clinical utility.